Good evening, good afternoon, and good morning. Welcome to the HUTCHMED conference call. At this time, all participants are on a listen only mode. After the speaker presentation, there will be a question and answer session. Please be advised that this call will be recorded. I will turn the call over to our first speaker today, Mark Lee, Senior Vice President of Corporate Finance and Development. Please go ahead. Thanks, Regina. Thank you everybody for attending the HUTCHMED conference call today to discuss the FDA update on surufatinib's NDA in neuroendocrine tumors. As most of you know, we issued a press release two hours ago detailing this current status, and it's on our website. A replay of this call will be available after this concludes. Today we have on the call our executive management team, Dr. Weiguo Su, Chief Executive Officer and Chief Scientific Officer, Dr. Marek Kania, Managing Director and Chief Medical Officer of HUTCHMED International, Johnny Cheng, our Chief Financial Officer, and Dr. Karen Atkin, our Chief Operating Officer. Before we begin, I would like to remind everybody that some of these statements on the call today may be considered forward-looking within the meaning of the safe harbor provisions under the U.S. Private Securities Litigation Reform Act of 1995. For further discussions on these risks, you can see our filings with the U.S. SEC on LSE AIM and on the Stock Exchange of Hong Kong. We are under no obligation to update the information today. With that, I would like to turn the call over to Weiguo Su. All right. Thank you, Mark, and everyone for joining this call. As disclosed in our announcement this morning or this evening, Asia time, the FDA issued a complete response letter or CRL regarding the NDA for surufatinib for the treatment of advanced endocrine, neuroendocrine tumors or NETs. The FDA essentially determined that at this time, the current data package does not support an approval in the U.S. In the CRL, the FDA concluded that the results from the two standard randomized placebo-controlled trials conducted exclusively in China and the U.S. bridging study together were not sufficient to support the determination of applicability to the U.S. population or U.S. medical practice, essentially requiring a MRCT to support the approval in the U.S. At this point, we will continue to work with the FDA in a collaborative effort to bring surufatinib to patients in need as soon as possible. This FDA action has no impact on ongoing or planned studies, which are well-funded by our existing cash balance in excess of $1 billion at year-end of 2021, potentially supplemented by non-dilutive funding options. We remain confident about the clinical value of surufatinib for NET patients and are committed to making surufatinib available to patients globally. There are very few treatments approved and used in these rare diseases, and patients and physicians will benefit from more options to address the unmet medical need. I would like to thank our patients and investigators for participating in the trials, including those in the U.S. bridging study. Patients who are receiving benefit from surufatinib clinical trials will continue to receive surufatinib. Ongoing surufatinib studies are proceeding as planned. I would also like to acknowledge our surufatinib NDA submission team, whose interactions with FDA were professional, highly competent, and of the utmost integrity. I will now ask Marek to provide further details on surufatinib and our development strategies in the U.S. Marek? Yeah. Thank you, Weiguo. Good morning, good afternoon, and good evening, everyone. I would like also to express my gratitude to patients and investigators participating in surufatinib trials. We will continue to work with FDA in very collaborative efforts to bring surufatinib to patients in need as soon as possible. Like Weiguo and everyone at HUTCHMED, I am very disappointed that data contained in our surufatinib NDA was not sufficient for FDA to find the standard result to be applicable to U.S. population and medical practice, as well as grounds for regulatory flexibility in this rare disease with very limited options. The safety and efficacy of surufatinib, an oral inhibitor of angiogenesis and immune modulation, was demonstrated in SANET-p and SANET-ep studies. Two randomized double-blinded phase 3 trials in patients with advanced pNET and epNET, which were conducted in China. surufatinib was approved in China for the treatment of epNET and pNET in December 2020 and June 2021 respectively. Results of HUTCHMED-sponsored bridging study, which is conducted in the United States and most recently presented at ASCO 2021, suggest similar safety and efficacy of surufatinib study populations in China. For approval, we have now been informed that the FDA requires a multi-regional clinical trial, called MRCT, which includes subjects more representative to U.S. patient population and aligned to U.S. current medical practice. In addition, pandemic-related issues concerning effects on scheduling as well as access contributed to this FDA action. This action by the FDA is not related to any safety issues with surufatinib, nor is it related to any issues in the conduct of the clinical trials or manufacturing of surufatinib. During the pre-submission meeting called pre-NDA meeting, discussions with the FDA on selpercatinib in May 2020, FDA agreed that a completed SANET-ep and SANET studies, along with the existing data from selpercatinib in U.S. non-pancreatic and pancreatic NET patients, could form the basis for support to U.S. NDA submission. Further, the FDA granted Fast Track designation for both NET indications in April 2020, now acknowledging the unmet need in this very difficult disease, difficult to treat patient population. The FTD status entitle us to use rolling submission as the basis for our NDA preparation. The selpercatinib rolling NDA submission was initiated in December 2020 and completed in April 2021, and was accepted and validated in June 2021. In line with our transparent and collaborative approach to working with regulatory agencies, we have submitted all U.S. patient data to FDA, along with extensive real-world evidence data. We believe this data supports the applicability of SANET results to U.S. population and medical practice, as well as grants regulatory flexibility. Those views are also shared by many thought leaders in that space. We are working and will continue to work with FDA to evaluate next steps and remain focused on ensuring the medicine is available globally to patients with this high unmet medical need. For the EMA, our surufatinib MAA is in a late phase review and applies for Japanese efforts, a Japanese bridging study. We have finished our first stage enrollment in this study and are preparing for stage two of this Japanese study. This effort will continue as planned and will provide further updates in due course. Meanwhile, the international selpercatinib team is continuing to execute on several ongoing studies, including combination studies with our partner BeiGene across multiple cohorts such as MET, metastatic colorectal cancer, small cell lung cancer, which are in advanced stages of enrollment. In addition to selpercatinib and savolitinib, which is led by AstraZeneca outside of China, the international teams progressing five potential new medicines across solid tumors and hematologic malignancies in various stages of development. For solid tumors, this includes fruquintinib, which is currently in a registrational multi-regional clinical trial, FRESCO-2 study, underlining our commitment to the highest possible standards in data generation. For hematological malignancies, those include our PI3K delta inhibitor, amdizalisib, our SYK inhibitor, savolitinib, our IDH1/2 dual inhibitor, HMPL-306, and our third generation BTK inhibitor, HMPL-760, which IND has been just recently cleared by FDA a few months ago, and we are in the process of study activation. Our development strategy in it for fruquintinib and amdizalisib is highly representative of our approach to bringing our innovative drug candidates to global markets. The fruquintinib FRESCO-2 randomized controlled study completed enrollment of more than 690 patients of colorectal and metastatic colorectal cancer patients across 14 countries in 165 sites in December 2021, and it happened during COVID pandemic ahead of schedule. The primary endpoint of this study is overall survival and event-driven endpoint, which will determine our final outcome. Our best estimate at this time is to read out this study in the second half of 2022. With every study initiated by HUTCHMED in the U.S., Europe, Japan, we consulted with regulatory global agencies on this trial design as well as regulatory strategy before commencing this phase 3 work. If positive, FRESCO-2 results would be used to support fruquintinib registration globally in U.S., Europe and Japan, along with positive original FRESCO-2 study, which led to approval in China, as well as ongoing U.S. phase 1 study that is most recently presented at ASCO GI in January. Similarly, the FDA recently provided clear thoughts on PI3Kδ inhibitor class. We'll continue to accrue patients in our amdizalisib US Delta expansion cohorts study, which has been currently significantly expanded, as well as our China phase two registration intent study. Our current development plan is to address new regulatory guidance in this class, and we'll work closely with the FDA to gain a full agreement before embarking on the registration trial that meets their requirements in the United States. In tandem with its long-term multi-asset global development strategy, we continue to routinely conduct global clinical trials in multiple geographies to ensure generation of data that is representative of the relevant population and work in a collaborative way and proactive way with regulatory bodies in various markets. This will conclude my remarks, and I will turn it back to Weiguo. Okay, thank you, Marek. Obviously we concur with the FDA on the value of MRCTs. I think this is actually our, you know, standard approach or baseline approach for registration internationally. As a matter of fact, FRESCO-2, our global phase three trial in metastatic CRC is a clear example of this approach. Marek just outlined how this applies to our late-stage compounds such as fruquintinib, amdizalisib, and so forth. We also plan to engage the regulators in the next 6-12 months on a global registration of savolitinib in collaboration with our partner, AstraZeneca. As previously disclosed, a global registration study is underway for savolitinib in NET-driven advanced papillary renal cell carcinoma since last fall, the SAMETA study. A global registration study of savolitinib in combination with AstraZeneca's Tagrisso or SAVANNAH study has been just initiated for patients with EGFR mutated, MET amplified, locally advanced or metastatic non-small cell lung cancer who have progressed on first line treatment of Tagrisso as the most recent therapy. All these are actually MRCT in design. Of course, it goes without saying that all the points raised by FDA are unrelated to the robust clinical efficacy and safety data in our clinical trials that led to our successful approval and commercialization in China. HUTCHMED is one of the first China-based biotechs to expand globally, and we are committed to pursuing our long-term multi-asset global development strategy. We are a well-funded large portfolio company, and our global R&D organization is advancing a diverse set of promising medicines that have the potential to evolve the standard of care in cancer, where unmet medical need remains high. Our commitment to this purpose and to our future as a global biopharma business is unchanged. I will now turn this call to Mark. Okay, thanks, Weiguo. Regina, can you please begin the Q&A session? Certainly. Ladies and gentlemen, we will now open for questions. If you'd like to register for a question, please press star one on your telephone. Thank you. Once again, ladies and gentlemen, that is star one for questions. Our first question comes from Louise Chen with Cantor. Please go ahead. Thank you. Hi. Thank you for hosting the call this morning, and thanks for taking my questions here. I had a few for you. First question I had for you is if you're gonna continue to invest in your U.S. infrastructure even though a commercial launch is delayed relative to initial expectations, at least that we had. What do you have set up in the U.S. thus far? Second question I had for you was on your selpercatinib application progressing in the E.U. and Japan. Why wouldn't the FDA issue be a potential complication in those areas of the world? What is the timing in terms of potential approval there? Last question, I just wanted to confirm that you will continue to pursue this MRCT for selpercatinib as well in the U.S. How long do you think it will take if you are planning to do that? How much do you think it'll cost you? Thank you. Like, Weiguo, do you want me to address it? Yeah. You would like to start? Yes. No, I think Marek, you can take these questions. Okay. Great. Louise, thank you for this question. Let me maybe start with kind of regulatory aspects, then I will address your commercial question. You know, as we said, we will continue working with FDA. We'll define next detailed path. Obviously, I'm going to refrain from speculation on exact timing. It's all subject for study design, which will definitely take very proactive and collaborative effort with U.S. FDA. We remain committed to NET patients. We truly believe those patients are in need, and we've seen it for last two years working with experts, advocacy groups, and that's the reason we are so committed. We'll have to define path which will be acceptable to U.S. FDA. That's what I will say for now. We'll update you in the next coming weeks or couple of months as we go through those discussions. A question about MAA in Japan. We are in the late phase of a review in MAA. Your question, will this impact other agencies' decision? I'm not going to speculate, as you know, they do collaborate in a transparent way. At the same time, every agency is proud of making independent assessment and decisions. I will leave it there. Timing in Europe again is dependent on agency ability to complete their inspections, which will have to happen across the GMP as well, the GCP. Timing of this unfortunately will be driven by lockdowns in China, as EMA does not have presence in China, so they will have to really travel. That's kind of evolving. As far as Japan, we are in the conduct of so-called bridging study in Japan. It will depend on our part two we're conducting. Hopefully, the study will complete in the second half of the year, and we'll be assessing our next steps for PMDA in due course, likely next year. Now, as far as your question about our existing capabilities in commercial spaces, you know, we are ready, and we are ready to launch. At the same time, we're anticipating significant outcome in FRESCO-2, which is just, you know, anticipated in the second half of this year. This will trigger our positive outcome, will trigger our NDA submission across U.S., Europe, and then shortly after in Japan. Japan participates in FRESCO-2 study, so this will be truly global effort. We definitely will continue building and bridging those capabilities into a near-term launch readiness efforts as well as utilizing our talent, you know, in the most efficient way. We built a strong but small team in the commercial space. We're looking number of options how to optimize that, you know, great talent and create value for patients and stakeholders as well. Did I answer all of your questions, Louise? Yes. Thank you very much. Thank you. Our next question comes from Alec Stranahan with Bank of America. Please go ahead. Thank you. Hey, guys. Thanks for taking our questions. Two from us. First, could you give a bit more detail on the comments from the FDA regarding aligning with the current U.S. medical practice? Was this use of savolitinib the primary driver here or something else like patient staging? Second, can you talk a bit more about the pandemic-related issues concerning the inspection scheduling and access? Is this something that is also impacting, your other programs? Thanks. Yeah. I'll let Marek answer the first question, and I can take on the pandemic issues in China. Marek? Yeah. Thanks, Weiguo. You know, without going into too much details, as you know, the U.S. or any other regulatory agency always looks at this representativeness of, let's say, real-world data into a local clinical practice. What I can say, you know, sitting in this space for quite some time, the NET space is broadly similar with the level of issues, gaps, unmet medical needs. There are some differences, obviously, resulting from new entries to this space, you know, when Afinitor or Sutent was approved across different geographies, which potentially create some differences. Broadly speaking, based on our large data, there's broad similarities of low utilization of this available and approved options. It's actually quite consistent across U.S., Europe and China. In China, the approvals of TKI came a little bit later than Western geographies. Broadly speaking, you know, you're talking about less than 10% of utilization of TKIs in all NET space and around 20% in stage 3 and 4 NET. Again, that highlights that unmet medical need. Having said that, you know, our view from the POs', the regulatory perspective, you know, the looking at more representative mix of population and the patient data coming from international studies rather than one country, and that's our position. That's what I would say about that. Weiguo, as far as COVID related. Yeah. You know, yeah, maybe you can address that. I think, you know, Marek has pointed out already, right? I think, we all know, neuroendocrine tumors are a very complex group of diseases, right? The fact that the U.S. FDA granted surufatinib with a Fast Track designation clearly acknowledged that, you know, there's a very strong unmet medical need in this field. With regard to COVID and issues in China, it's basically all related to, you know, travel restrictions or restriction to access to the facilities, both hospitals and/or clinical centers or manufacturing sites. We had, you know, actually completed two inspections late last year, but the two remaining inspections are really challenged by the COVID and the restrictions imposed on travel and also access to some sites. You know, for instance, Suzhou. When Suzhou was closed, our manufacturing facility was closed as well. At the moment now, Shanghai is completely in a lockdown. It's been, you know, quite difficult. You know, with regard to other programs that we are conducting in China, you know, a lot of trials are ongoing, so we are, you know, managing the best we can to minimize the impact on ongoing trials. Certainly, you know, site initiations and new study initiations, there are some impact on some of these activities. Again, we're shifting a lot into online, even, you know, site initiations are done online now. We are trying to really manage through this difficult period in China. I may add a perspective from outside of China. I must say, as you know, demonstrated in FRESCO-2 global, truly global first global study we conducted, truly global across three continents, that was demonstration of you know, ability to execute during COVID. You know, that was whole last year where different countries were in different restrictions. From international point of view, I don't see a really major impact as of now. You know, Western world is coming back kind of to so-called new normal. I think site investigators, oncologists you know, learn how to adapt this to this new reality. There's no material impact on international sites in the conduct of our studies. Great. Thank you. Thank you. Our next question comes from Yang Huang of Credit Suisse. Please go ahead. Thank you. Thanks. I have three questions. First of all, it seems to me management is not surprised with the CRL, as management appear to completely agree that MRCT is the way to go. Given FDA kind of agreed before we submit our NDA that the China phase 3 and the bridging study can form the application basis. It’s a little bit like some of our fellow China biotech companies that the view on drug application from China has changed no matter it’s a broad indication or kind of off indication. Is that the case here? No, I can provide my- If you want me to address it or you want. Yeah. I'll provide my comments, and Marek, you can chime in as well. Sure. Obviously, you know, this is an evolving landscape here we are talking about. Certainly when we initially discussed with the U.S. FDA, you know, prior to the filing, you know, we got alignment with the U.S. FDA that the data package we proposed and that we submitted ultimately could have formed the basis to support the NDA. But it's been evolving as you know. I think MRCT obviously is the highest standard, most objective to assess. You know what I mean? Obviously, this is a review issue. We really can't comment too much on. You know, I can understand the rationale behind it, obviously, Chinese patients versus U.S. patients, although we've done extensive bridging studies and demonstrating in terms of efficacy and safety and also PK as well, completely consistent across different areas. Really can't speculate too much on, you know, China versus U.S. here. You know, we are not in a position to provide any comments on this topic really. Really on the MRCT, you know, everyone knows, right, it's the most comprehensive, most objective assessment. You know, you can't argue with that except that, you know, we did have alignment with U.S. FDA when we submitted. As I say, as I just alluded to, right, this is a kind of evolving area. You know, FDA can always adjust their policies. I guess it depending on the, you know, the data they have, they have the full view of the landscape, right? Yeah. I don't know if Marek has anything else to add to this. No, like, well said. What I would say, you know, obviously, this is rare disease where, you know, we, I can't even see any other case similar to this, where two randomized phase 3 studies has been generated in China or any other single country in, you know, with level one evidence. That's the reason we were so motivated, as well as experts in the field, that this should be considered as an option, hence we engaged with U.S. FDA two years ago. I think this package still remains as one of the strong in that space. We'll definitely continue working with U.S. FDA to define path as next step and, you know, comply with current views from regulatory point of view. I hope we answered your question. Okay. Got it. Yeah, thanks for the color. My second question is about the potential design of this MRCT. I understand we are still going to discuss with the FDA post the CRL, and we'll probably get some more idea and input what kind of MRCT the FDA wants us to conduct. For us, I mean, do we think our China phase 3 trial design will be enough for potential MRCT design? Just we change the patient population, right, from China to other countries, but otherwise the trial design can be quite similar, or we think there could be more to be done in MRCT? Well, I guess, do you want me to address that? Yeah. No. Yeah, let me say just, you know, briefly that, at the moment, you know, we are still formulating our plan. Certainly everything needs to be discussed and aligned with the FDA prior to the initiation. Details to be worked out and to be agreed upon with the U.S. FDA. Yeah, Marek, please add in. Yeah. What I will only add to this, we will do definitely international studies, whatever design we agree, and we have several options to consider, which I'm not ready to speculate at this point. We'll try to not just repeat, but to complement existing level of evidence, because otherwise it would be unfortunately, you know, use of very scarce, you know, patients in clinical trial setting. We'll work it out in the most constructive way, so it can complement over our package. We'll update, you know, investor community, you know, in the right time or when we are ready to speak specifics. Okay, got it. Yeah, my last question is about also related to the COVID situation in China. I want to understand what's the potential COVID impact to our commercial activities in the first quarter and the second quarter? Are we seeing some, you know, potential drug sales impact because of COVID, because of lockdown? Thanks. Well, at the moment we are doing fine. First quarter, you know, was not impacted much. Second quarter, particularly in April in Shanghai, you know, obviously the lockdown makes it more difficult. What we do is we shifted a lot of commercial activities and, you know, a lot of seminars and doctors' visits, all now online, so it's all conducted virtually now. Certainly, you know, how effective this is so far seems to be, you know, to our satisfaction. We were a bit lucky in hindsight that we have a pretty large inventory well into second half. On that side, we are okay. The logistics or distribution is not impacted by much at the moment. At the moment, we see, obviously, you know, these travel restrictions will, you know, here and there, right? Like, you know, it was in Northeast and now in Shanghai, to some extent in Guangzhou and Shenzhen. We'll have some impact on, you know, on patients in particular, going to the hospitals and to visit their physicians and so forth. But so far, you know, our early assessment is, you know, we are managing it quite well. Okay. That's good to know. Thanks a lot. Johnny, can you do to add? Let me No, I think yes, exactly per what you just said. I think we are continuing, you know, observing the situation. So far, just like Weiguo said, we are managing. The team has been managing quite well. Okay, great. Thanks. Thanks. Thank you. Our next question comes from Katie Xu of Jefferies. Please go ahead. Thank you. Thank you for taking my questions. In your view, what is the broad implication on China-developed drugs using bridging studies to gain U.S. approval based on Chinese experience? Also, any alternative trial design or scale of the bridging study could have changed outcome? Thanks. Maybe I'll ask Marek to provide his thoughts and first. Okay. Thank you, Weiguo. You know, to answer your question, our core strategy is actually across all development programs of all entire portfolios to conduct multi-regional studies. That's the reason why we are building very robust and very experienced and talented team in development like regulatory operations, and you name it. That's our baseline approach. The FRESCO-2 is one of the first global development trials as an example, and that's our baseline. Surufatinib is a case as we discussed before, is very unique, two positive studies in a rare disease, where there's high interest in the outcome of this to change clinical practice. That's the reason why we took this in a way as a legacy program, our older program, and to find the right path. We'll continue to do so. Across other programs, if I don't see personal implication on our portfolio, this outcome or this specific NDA as a, you know, a policy outcome. I'm not going to comment what outcome of this or similar decisions will be to other biotech sponsors, but, I'm focusing on our strategy here. I hope it addresses the change. I don't see this as an implication to broader portfolio at all because we, you know, again, we continue investing across seven active programs and soon to be more with our ongoing IND preparations to expand our portfolio. Weiguo, anything to add to this? No, I think you kind of covered it mostly. I think it's all case by case, right? The requirement of MRCT appears to be now by the U.S. FDA and maybe, you know, globally. In the future, it's either China being, you know, joining the global trials or maybe we do it separately or in parallel. It all depends on, I think, case by case, right? Depending on the patient population, depending on standard of care. All of these need to be taken into consideration. You know, for sure, that may be obviously, I think it is clear that an MRCT is required for U.S. registration. Thank you very much. I also have a follow-up, if I may. How different is the treatment paradigm for pNET and non-pNET in China versus in the United States? Thanks. Okay. Well, certainly now, both, I mean, Sutent is for the pancreatic and Afinitor also, pNET and the gastric and lung. I think they're both available today, anyway, in China and the U.S., although a few years ago, a few years back when we initiated the phase three SANET trials, they were not broadly available in China, certainly not listed or reimbursed by the NRDL. Today, I think both agents are broadly available. The issue is, I think in the U.S., there may be now like Lutathera has been approved for, you know, only for the SSA-expressing tumors, and you know, used rather narrowly by the patients, which is not available in China yet, although not available broadly in China. I think it is not easy to administer because of the radioactivity. I think I would just say they are relatively today the SOCs between the two countries are relatively similar. It's obviously, you know, very complex disease. I think the hallmark is that it's just very complex. There are, you know, almost every organ, every tissue can have a neuroendocrine tumor. They respond to treatments differently. That is, you know, the other thing is that these tumors, they are, you know, they don't grow very fast, but they're not easy to treat. They progress, they move on to something, and if the patients move on to something else, but, you know, they progress again and they tend to live for many years and they very quickly can just run out of options or treatment options. I think there is a very high unmet medical needs for these patients. Anything else, Marek, you can add, or Xiaoming? Okay. Okay. No, I think you covered as well. You know, as I think I looked at earlier as of actually just a few weeks ago, there was publication in Europe actually by independent NET experts from ENETS, actually. Europe is even more heterogeneous across different countries. Again, based on 10,000 patients, you know, registry, that highlights really that what I was saying, broad similarity of low utilization, low number of options and patients in the need of, you know, new options. I think that's consistent in across any region. Thank you. Thank you. Our next question comes from John Newman with Canaccord. Please go ahead. Thank you. Hi there. Good evening and thank you for taking my questions. I have two questions. The first question I have is going forward, in terms of your randomized studies that will include U.S. patients for surufatinib and NETs, might it be possible to run a study covering both PNETs and epNETs, or would you simply look to replicate the studies that were run in China? The second question I have is more general, and it is, there's been a lot of questions around approval of drugs developed in China by the FDA. I wonder if the FDA is simply following the path that it has always followed, which is the agency seems to have always preferred to have studies in U.S. patients just so that they can be comfortable with differences in genetic backgrounds. I'm just wondering if this is just an extension of that. I believe Dr. Pazdur was actually quoted after the Eli Lilly decision as saying that the FDA has nothing against drugs being developed in China. They just would like to see that the results are generalizable. Just curious if this is just an extension of a policy that's actually been in place for a very long time and not specific to China at all. Thank you. Thanks, John. I'll ask Marek to provide his thoughts first on your two questions. Marek? Yeah. Thank you, Weiguo. John, very good question. Obviously, deep question as well. First of all, I think your statement about the U.S. FDA always requested or expected sponsor to provide the representative data package, correct? I think from that perspective, Dr. Pazdur's statement is kind of in line with that. You know, discussion about one country versus regulations or statement in the record, there was nothing. I think as of today, except this recent discussion about MRCT, there's no regulation specifying, you know, X number of patient or percentage of patients must be in U.S., FDA never had that bright line. It's always, you know, totality of the data, assessment, and so on. In principle, you're totally correct. I think in this specific, you know, history as you now go back to three years ago, where Dr. Pazdur, you know, made statement at ASCO on saying, "Hey, bring it on," if as long as applying, you know, simply addressing high unmet medical needs, high innovation, and so on. I think it's in a way prompted that maybe, you know, more busy wave of new applications. In principle, I think you're right. FDA always is looking for representative population. You know, again, going back to the specific NDA discussion, we had that discussion in a very transparent way. The data packets didn't change since, you know, our application and pre-NDA discussion. I hope it answers your broad question actually. I'm happy to venture anywhere else you want me to go. Yes. Thank you. John, with regard to the study design, whether we combine everything or we do separately, obviously, you know, we are still at the stage, you know, to formulate our ideas or plans. We still need to discuss with the agency on such as MRCT design. But I think the challenge is, so certainly if we combine everything together, would be the most preferable. I think the challenge is, whether you can properly stratify all these different diseases in, you know, properly balance. Yeah. Anyways, a lot to brainstorm and discuss with the agency. Okay, great. Thank you. Thank you. Our next question comes from Paul Choi with Goldman Sachs. Please go ahead. Thank you. Thank you, and good evening and good morning to everyone. Two questions from us, please. First, with regard to maybe expanding on thoughts on trial design here, would it maybe perhaps make more sense for you from a development perspective in terms of designing a multinational randomized controlled trial to think about specific subpopulation? And then also on that note, how do you think about, you know, potentially stratifying for, you know, lutetium or Lutathera radiotherapy-treated patients? Would that be a particular, you know, subgroup that you would focus on? Or, in fact, how would you factor that into a potential clinical trial design? My second question is with regard to the broader pipeline and specifically with development of amdizalisib, your PI3Kδ. Does the message or the results from today's FDA decision, you know, alter your thinking with regard to designing PI3Kδ? I ask that question also in the context of recent, you know, FDA adcoms and feedback on other drugs in this particular category. Thank you very much. Thanks, Paul. Again, Marek, can you Yeah. Thank you for this first question. While I go, I'm happy to address those, but I will pause after the surufatinib design question. You know, it's the same what Weiguo said related to prior question. All ideas on the table. I think what we'll be exercising here obviously if we run one study, obviously well-controlled and stratification factors in a prioritized way. You know, simple repetition of existing study would be very challenging, but we'll find a way of meaningful design which will address still existing options and meet regulatory goals. I think between your question and John's question, those are very similar kind of line of strategic thinking. Again, I will refrain from specifics. Your example, I think it's a good one. You know, we'll be definitely exercising different prior therapies and how we control for that variability, especially if we combine NET and pNET in one trial. Weiguo, do you want me to address the PI3K, or you want to- Sure. Comment on this? No, go ahead. Go ahead. Yeah. Obviously we were part of a very careful listening of ongoing discussions in this call. As I said in my opening remarks, it's in a way almost perfect timing for our development stage of development as we are expanding our ongoing study to address those dose findings and we heard FDA is looking for a really creative way of identifying the lowest effective dose and mitigate any potential class effect, the toxicity concerns. At the same time, you know, developing study in such a way so they can look carefully in the evaluation of survival assessments in a descriptive way, not primary endpoint. You know, there are several implications of most recent ODAC driving our development. Doesn't change it in a drastic way as we were on the way of, you know, number of discussions in exactly the same line, how we bring the highest level of efficacy of our, you know, well-engineered profile of our assets. You know, we control well short-term, long-term toxicities, and we can demonstrate this in the most robust data package before we embark on a registration comparative study. That's exactly what we are doing at this point. We'll be engaging with FDA most probably very soon in actually a response to ongoing discussions. Again, that's one of those so-called global in mind development efforts we will be taking while everyone is trying to reclassify their strategies in this class, very important for patients. Thanks, Marek. Great. Thank you very much for taking our questions. Yeah. Thank you. I was just going to add, I think this is a very timely advisory meeting because amdizalisib we've been, you know, at the moment basically are looking to move into a registration study. This ODAC provided certainly, you know, additional advice or guideline to industry, basically. I think, you know, certainly it's very timely and, hopefully we, you know, as Marek said, we are formulating our plans and will engage with the U.S. FDA to get alignment. Secondly, you know, we are quite confident about amdizalisib safety profile and, you know, it's a compound designed to improve safety profile to reduce toxicities, particularly liver and GI toxicities associated with the first generation compounds. You know, the data we have generated so far seem to be quite favorable. We are quite confident. Anyways, the bar has been raised by the FDA and, you know, I think it's good that we have an opportunity to demonstrate fully that amdizalisib will stand out. Anyways, we'll work with the FDA and finalize our plan and move forward with. Thank you. Thank you once again, ladies and gentlemen. If you'd like to register for question, please press star one on your telephone. Thank you. Once again, ladies and gentlemen, that is star one for questions. Mr. Lee, there seems to be no further question at this point in time. Thank you. Thank you, Regina. Okay. Well, thank you everyone for joining. Weiguo, do you have any closing remarks or? No. Obviously, you know, this, you know, it's a disappointing news to us, but we are fully committed to bring surufatinib to patients. You know, we are confident surufatinib has a unique MOA and the data to date demonstrate its clear clinical benefit to patients. You know, we'll be engaged with the U.S. FDA and get clarity on the registration path or study design going forward. Thank you all. Thank you. Thank you, operator. Thank you. Thank you. Yep. Thank you. Thank you for your participation. This concludes the conference. Goodbye. Bye-bye.