HUTCHMED (China) Limited (HCM) Earnings Call Transcript & Summary

Good evening, good afternoon, and good morning. Welcome to the HUTCHMED conference call. [Operator Instructions] 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 2 hours ago detailing this current status, and it's on our website. This call -- a replay of this call will be available after this concludes. So 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. And before we begin, I would like to remind everybody that some of the statements on the call today may be considered forward-looking with the meaning of the safe harbor provisions under the U.S. Private Securities Litigation Reform Act of 1995. And for further discussions on these risks, you can see our filings with the U.S. SEC, on LSE's AIM and on the stock exchange of Hong Kong. And we have our understanding no obligation to update the information today. So with that, I would like to turn the call over to Weiguo.

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 to the treatment of advanced 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. The CRL, the FDA concluded -- in the CRL, the FDA concluded that the results from the 2 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. And 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 ended 2021, potentially supplemented by nondilutive 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?

Yes. 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 trial. 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 else at HUTCHMED, I'm very disappointed that data contained in our surufatinib NDA was not sufficient for FDA to find the standard result. It could be applicable to U.S. population and medical practice as well as ground for regulatory flexibility in the rare disease with very limited options. The safety and efficacy of surufatinib, an oral inhibitor of angiogenesis and immune modulation, was demonstrated in the SANET-p and SANET-ep studies, 2 randomized double-blinded Phase III trials in patients with advanced pNET and epNET, which were conducted in China. Surufatinib was approved in China for the treatment of epNETs and pNETs 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, suggests similar safety and efficacy of SANET study population in China. For approval, we have now been informed that FDA requires a multiregional clinical trial called MRCT, which includes subjects more representative to U.S. patient population and aligned to U.S. kind of medical practice. In addition, pandemic-related issues concerning inspection 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 related to any issue in the conduct of the clinical trials or manufacturing of surufatinib. During the pre-submission meeting called pre-NDA meeting in different terms with the FDA on surufatinib in May 2020, FDA agreed that completed SANET-ep and SANET-p studies, along with the existing data from surufatinib in U.S. in non-pancreatic and pancreatic NET patients could form the basis for support to a U.S. NDA submission. Further, the FDA granted Fast Track Designation for both NET indications in April 2020 [indiscernible] acknowledging the unmet need in this rare disease difficult-to-treat patient population. The [ FTD ] status entitle us to use rolling submission basis for our NDA preparation. The surufatinib 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 for a [indiscernible] flexibility. Those views are also shared by many [indiscernible] in that space. We are working and we'll 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 as far for Japanese efforts, Japanese bridging study, we finished our first stage enrollment in the study, now preparing for Stage 2 of this Japanese study. These efforts will continue as planned, and we'll provide further updates in due course. Meanwhile, the international surufatinib team is continuing to execute on several ongoing studies, including the [ tislelizumab ] combination studies with our partner BeiGene across multiple cohorts such as metastatic colorectal cancer, small cell lung cancer, which are in advanced stages of enrollment. In addition to surufatinib and savolitinib which is led by AstraZeneca outside of China, the international team progressed 5 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 registration of multiregional 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 sovleplenib, our IDH1/2 dual inhibitor HMPL-306 and our third generation BTK inhibitor HMPL-760, which in the IND has been just recently cleared by FDA a few months ago, and we are in the process of study activation. Our development strategy for fruquintinib and amdizalisib is highly representative of our approach to bringing our innovative drug candidates to global market. Fruquintinib-FRESCO-2 randomized controlled study completed enrollment in -- of more than 690 patients of colorectal and metastatic colorectal cancer patients across 14 countries in 150 [indiscernible] 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 obviously determines our final outcome. Our best estimate at this time is to read out the study in the second half of 2022. As 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 III work. If positive, FRESCO-2 results would be used to support through continued registration globally in U.S., Europe and Japan along with positive original FRESCO-3 study, which led to approval in China as well as ongoing U.S. Phase I study that is most recently presented at ASCO GI in January. Similarly, the FDA recently provided clear thoughts on PI3K-delta inhibitor class. We'll continue to accrue patients into our [indiscernible] U.S. dose expansion cohort study, which has been currently significantly expanded as well as our China Phase II registration intent study. Our current development plan is to address the new regulatory guidance in this class, and we'll work closely with the FDA to gain a full agreement before embarking on the registrational trial as their requirements in the United States. [indiscernible] 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 MRCT. And I think that this is actually our standard approach or baseline approach for registration internationally. As a matter of fact, FRESCO-2, our global Phase III trial in metastatic CRC, is a clear example of this approach. [indiscernible] 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 to 12 months on the global [indiscernible] of savolitinib in collaboration with our partner, AstraZeneca. As previously disclosed, a global registration study is underway for savolitinib in MET-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 SAFFRON 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 saw actually MRCT in design. So 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-founded, 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?

[Operator Instructions] And our first question comes from Louise Chen with Cantor.

So I'd ask a few for you. First question I have for you is if you're going to continue to invest in your U.S. infrastructure, even though a commercial launch is delayed relative to initial expectations, at least that we had? And what you have set up in the U.S. thus far? And then second question I had for you was on your surufatinib application progressing in the EU and Japan. Why wouldn't the FDA issue be a potential complication in those areas of the world? And then what is the timing in terms of potential approval there? And then last question, I just wanted to confirm that you will continue to pursue this MRCT for surufatinib as well in the U.S. How long do you think it will take if you are planning to do that? And how much do you think it will cost you?

Weiguo, do you want me to address it? Or you would like to start?

Yes. No, I think, Marek, you can take these questions.

Okay. Great. Louise, thank you for this question. So let me maybe start with kind of regulatory aspects, and I will address your commercial question. As we said, we will continue working with FDA. We'll define next detailed path. So obviously, I'm going to refrain from speculation on exact timing. It's all subject for study design, which we'll definitely take a very proactive and collaborative efforts with U.S. FDA. We remain committed to NET patients. We truly believe that patients are in need, and we've seen it for the last 2 years working with experts [indiscernible]. And that's the reason we are so committed. So we have to define path which will be acceptable to U.S. FDA. So that's what I will say for now. We'll update you in the coming weeks or a couple of months as we go through those discussions. Question about MAA in Japan. We are in the late phase of review in MAA. Your question, will this impact agency -- other agency's decision. I'm not going to speculate, as you know, they do collaborate in a [ transformed ] way. But at the same time, every agency is proud of making independent assessment and decisions. So 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 [indiscernible]. And timing of this, unfortunately, will be driven by lockdowns in China. EMA does not have a presence in China, so they will have to really travel. So that's kind of evolving. As far as Japan, we are in the conduct of a so-called bridging study in Japan. So it will depend on our Part 2 we're conducting. Hopefully, this study will complete in the second half of the year, and we'll be [indiscernible] in due course likely next year. Now as far as your question about our existing capabilities in commercial space, we are ready to launch. At the same time, we're anticipating a significant outcome in FRESCO-2 [indiscernible] anticipated in the second half of this year. This will trigger -- our positive outcome will trigger our NDA submission across the U.S. and 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 bringing those capabilities into near-term launch, readiness efforts as well as utilizing our talent in the most efficient way. We built a strong but small team in the commercial space. So we're looking at a number of options how to optimize that great talent in the trade value for patients and stakeholders as well. Did I answer all your questions, Louise?

Yes.

Our next question comes from Alec Stranahan with Bank of America.

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 [indiscernible] the primary driver here or something else like patient staging? And second, can you talk a bit more about the pandemic-related issues considering the inspection scheduling and access? Is this something that is also impacting your other programs?

Yes, I'll let Marek to answer the first question, and I can take on the pandemic issues in China. Marek?

Yes. Thanks, Weiguo. So without going into too much detail, as you know, the U.S. or any other regulatory agency always looks at this representativeness of, let's say, industry foreign data into a local clinical practice. What I can say sitting in this space for quite some time, NET space is broadly similar with the level of issued gap [indiscernible]. And there are some differences, obviously, resulting of new entries to this space when [indiscernible] was approved across different geographies, which potentially creates 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 the U.S., Europe and China. In China, the approvals of TKI came a little later than Western geographies. But broadly speaking, you're talking about less than 10% of utilization of TKIs in all NET space and around 20% in Stage 3 and 4 NET. So again, that highlights that unmet medical need. Having said that, obviously, from the [indiscernible] regulatory perspective, FDA is looking at more representative mix of population and the patient data coming from international studies rather than one country. And that's in position -- that's what I would say about that. Weiguo, as far as COVID related -- yes, maybe you can address that.

I think Marek has pointed out already, right? I think we all know neuroendocrine tumors of a very complex group of diseases, right? The fact that the U.S. FDA granted surufatinib with a Fast Track Designation clearly acknowledge that 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 travel restrictions or restriction to access to the facilities, both hospitals and/or clinical centers or manufacturing sites. So we actually completed 2 inspections late last year, but the 2 remaining inspections are really challenged by the COVID and the restrictions imposed on travel and also access to some sites. For instance, Suzhou, when Suzhou was closed, our manufacturing facility was closed as well. At the moment now, Shanghai is completely in a lockdown. So it's been quite difficult. With regard to other programs that we are conducting in China, a lot of trials are ongoing. So we are managing the best we can to minimize the impact on ongoing trials. Certainly, site initiations and new study initiations, these saw -- there are some impacts on -- there was some impact on some of these activities. Again, we are doing -- shifting a lot into online. Even site initiations are done online now. And so we are trying to really manage through this difficult period in China.

If I may add a perspective from outside of China, I must say it demonstrated in FRESCO-2 global -- truly global -- first global study we conducted truly global across 3 continents. That was demonstration of ability to execute during COVID. That was all last year for different countries were in different restrictions. So from an international point of view, I don't see a really major impact as of now. Western world is coming back kind of the so-called new normal. And I think site investigators, oncologists learn how to adapt to this new reality. So there's no material impact on the international side into context of our studies.

Our next question comes from Yang Huang of Credit Suisse.

So I have 3 questions. First one, so it seems to me, management is not surprised with the CRL as management appear to completely agree that MRCT is the way to go. So given FDA kind of grade when we -- before we submit our NDA that 2 China Phase III and the bridging study can form the application basis. So it seems to -- it seems a little bit like our -- some of our fellow China biotech companies that they view drug application from China has changed, no matter it's a broad indication or kind of open indication. Is that the case here?

Do you want me to address it, or you want...?

Yes. I'll provide my comments and Marek, you can chime in as well. So obviously, this is an evolving landscape here we are talking about. And certainly, when we initially discussed with the U.S. FDA prior to the filing, we've got alignment with the U.S. FDA that the data package we proposed, and we submitted ultimately could have formed the basis to support the NDA. And -- but it's been evolving, as you know. I think MRCT, obviously, is the highest standard, most objective to assess. I mean, obviously, this is -- it's a review issue we cannot -- we really can't comment too much on. And I can understand the rationale behind it, obviously, Chinese patients versus U.S. patients, although we've done extensive bridging studies both and demonstrating both in terms of efficacy and safety and also PK as well, completely consistent across different areas. So I really can't speculate too much on China versus U.S., yes. No, we are not in a position to provide any comments on this topic really. Really on the MRCT, everyone knows, right? It's the most comprehensive, most objective assessment. You can't argue with that, except that we did have alignment with U.S. FDA [indiscernible]. But as I say, as I just alluded to, right, this is kind of evolving area. Now FDA can always adjust their policies. And I guess depending on the data they have -- they have the full view of the landscape, right? So I don't know if Marek has anything else to add to this.

No, Weiguo, well said. What I would say, obviously, this is a rare disease where we -- I can't even see the -- any other case similar to this where 2 randomized Phase III studies has been generated in China or any other single countries in -- with level 1 evidence. And that's the reason we are [indiscernible] as well as experts in the field that this should be considered as option. And hence, we engaged with U.S. FDA 3 years ago. And I think this market still remains as one of the strong in that space. And we'll definitely continue working with U.S. FDA to find a path as next step and comply with current views from a regulatory point of view. I hope we have answered your question.

Got it. Got it. Yes. My second question is about the potential design of this MRCT. I understand that we are still going to discuss with the FDA post the CRL, and we'll probably get some more idea and input to what kind of MRCT the FDA want -- potentially wants us to conduct. But for us, I mean, do we think our China Phase III trial design will be enough for potential MRCT design? Just we changed 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?

If I guess, do you want me to address it?

Yes. No. Yes, let me say just briefly that at the moment, we are still formulating our plan. Certainly, everything needs to be discussed and aligned with the FDA prior to the initiation. So details to be worked out and to be agreed upon with the U.S. FDA. Yes, Marek, please add in.

Yes. What I would only add to this, we will do definitely international study, whatever design we agree. And we have several options to consider, which I'm not ready to speculate at this point. But we'll try to -- not to just repeat, but to complement existing level of evidence because otherwise, there would be unfortunate use of [ very scared ] patients in the clinical trial setting. And we're working out in the most constructive way, so it can complement overall packet. But we'll update investors coming into -- in the right time when we are ready to [indiscernible].

Okay. Got it. My last question is about -- also related to the COVID situation in China. So 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 potential drug sales impact because of COVID but also lockdown?

Well, at the moment, we are doing fine. First quarter was not impacted in March. Second quarter, particularly in April in Shanghai, there was -- obviously, the lockdown makes it more difficult. What we do is we shifted a lot of commercial activities and a lot of seminars and doctors' visits all now online. So it's all conducted virtually now. Certainly, how effective this is so far seems to be to our satisfaction. We were a bit lucky on the hindsight that we have a pretty large inventory well into second half. So on that side, we are okay. And the logistics, the distribution is not impacted by much at the moment. So at the moment, we see -- obviously, this travel restriction as well here and there, right, still like it was in Northeast and now in Shanghai, to some extent, in Guangzhou and Shenzhen. So we'll have some impact on patients, in particular, going to the hospitals and the visit their physicians and so forth. But so far, our early assessment is we are managing quite well.

Okay. That's good to know.

Johnny, do you [indiscernible] to add?

No, Weiguo. I think yes, exactly what you just said. I think we are continuing observing the situation. But so far, just like we got -- we are managing -- the team has been managing quite well.

Our next question comes from Kelly Shi of Jefferies.

In your view, what is the broad implication on China developed drugs using bridging studies to gain U.S. approval based on previous experience? And also any alternative trial design or scale of the bridging study could have changed outcome?

Maybe I'll ask Marek to provide his thoughts and -- first.

Okay. Thank you, Weiguo. So to answer to your question, our core strategy is actually across all development programs, our entire portfolio is to conduct multiregional studies. That's the reason why we are building very robust and very experienced and talented team in development of the larger operations, and you name it. So that's our baseline approach. And the FRESCO-2 is one of the first global development trials as an example, and that's our baseline. Surufatinib case, as we discussed before, is very unique, 2 positive studies in rare disease where there's high interest in the outcome of this to change clinical practice. And that's the reason why we took this in a way as a legacy program, our older program and to find the right path. And we'll continue to do so. But across other programs, if I don't see personal execution on our portfolio is outcome for this specific NDA as 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 strategic here. So I hope it addressed the change. I don't see this as an implication to broader portfolio at all because again, we continue investing across 7 active programs and soon to be more with our ongoing IND preparation 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? But MRCT -- requirement of MRCT appears to be now by the U.S. FDA or maybe globally. So in the future, it's either China join the global trials or maybe we do it separately or in parallel. So it all depends on, I think, case by case, right, depending on the patient population, depending on -- of care. So all of these need to be taken into consideration. So for surufatinib, obviously, I think it is clear that an MRCT is required for U.S. registration.

I also have a follow-up, if I may. So how different is the treatment paradigm for panc NET and non-panc NET in China versus in the United States?

Okay. Well, certainly now both -- I mean, [indiscernible] is for the pancreatic and Afinitor also pNET and the gastric and lung. I think they're both available today, anyways, in China and the U.S., although a few years ago, a few years back when we initiated the Phase III SANET trials, they were not broadly available in China, certainly not listed or reimbursed by NRDL. But today, I think both agents are broadly available. The issue is, I think in the U.S., they may be now like Lutathera has been approved only for the SSA-expressing tumors and 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 radio activity. I think I would just say they are relatively today, the SOCs between the 2 countries are relatively similar. And it's obviously a very complex disease. I think the hallmark is that it's just very complex, almost every organ, every tissue can have neuroendocrine tumor. So -- and they respond to treatments differently. And the other thing is that these tumors, they are -- they don't grow very fast, but they are not easy to treat. They don't -- they progress, they move on to something [indiscernible] move on to something else, but they progress again. And they tend to live for many, many years. And they very quickly can just run out of options or treatment options. And I think there is a very high unmet medical need for these patients. Anything else, Marek, you can add, chime in here?

No, I think you covered this well. And I think I looked it earlier, as of actually just a few weeks ago, the publication in Europe actually by independent NET experts from [indiscernible] actually. Europe is even more heterogeneous across different countries. But again, based on 10,000 patients in the registry that highlight really that -- what I was saying broad similarity of low utilization, low number of options and patients in the new options. And I think that's the consistency across in the region.

Our next question comes from John Newman with Canaccord.

Two questions. The first question I have is going forward, in terms of your randomized studies that will include U.S. patients for surufatinib in 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 relative to China by the FDA. But 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. [indiscernible] was actually quoted after the Lilly decision as saying there's -- the FDA has nothing against drugs being developed in China. They just would like to see that the results are generalizable. So I'm 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.

Thanks, John. I'll ask Marek to provide his thoughts first on your 2 questions. Marek?

Thank you, Weiguo. John, a very good question, obviously, deep question as well. So first of all, I think your statement both on -- you said we always requested or expected sponsor to provide the representative data package, correct? And I think from that perspective, Dr. [indiscernible] statement is kind of in line with that. Discussion about one country versus regulations or statements in the regs, there was nothing. And I think as of today, except the recent discussion about MRCT, there's no regulation specifying X number of stational percentage of patients must be in U.S. FDA never had that [ track ] line. It's always a totality of the data, assessment and so on. But in principle, you're totally correct. I think in this specific history, as you now go back to 3 years ago where Dr. [indiscernible] made a statement at AACR, saying, hey, bring it on as long as applying -- simply addressing high unmet medical needs, high innovation and so on. So I think it's in a way prompted that maybe more busy wave of new applications. But in principle, I think you're right. FDA always is looking for representative population. Again, going back to the specific NDA discussion, we had that discussion in a very transparent way. This data package didn't change [indiscernible] pre-NDA discussion. So I hope it answers your broad question actually. I'm happy to answer anywhere else you want me to go.

So John, with regard to your study design, whether we combine everything or we do separately, obviously, we are still at this stage to formulate our ideas or plans. But we still need to get -- we need to discuss with the agency on such MRCT design. But I think the challenge is -- certainly, if you combine everything together would be the most preferable. But I think the challenge is whether you can properly stratify all these different diseases and properly balanced. Anyways [indiscernible] brainstorm and discuss with the agency.

Our next question comes from Paul Choi with Goldman Sachs.

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 a specific subpopulation? And then also on that note, how do you think about potentially stratifying for [ lutetium ] or Lutathera radiotherapy treated patients? Would that be a particular subgroup that you would focus on? Or in fact, how would you factor that into a potential clinical trial design? And then my second question is with regard to the broader pipeline and specifically with development of amdizalisib, your PI3K. Does the message or the results from today's FDA decision alter your thinking with regard to designing PI3K? I asked that question also in the context of recent FDA adcoms and feedback on other drugs in this particular category.

Thanks, Paul. Again, Marek, can you...

Yes. So thank you for this first question. Weiguo, I'm happy to address those. But I will pause after [indiscernible] design question. So it's the same what Weiguo said related to prior question. All ideas on the table. And I think what we'll be exercising here, obviously, is we run one study of the well-controlled and stratification factors in a prioritized way. 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, I think there's a very similar kind of line of strategic thinking. But again, I will refrain from specifics or example. I think it's a good one. We'll be definitely exercising different prior therapies and how we control for that variability, especially the combined NET and pNET in one trial. Weiguo, do you want me to address the PI3K? You want to comment on this?

Sure. Yes, go ahead.

Yes. So obviously, we were part of a very careful listening of ongoing discussions in this class. And 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 dose finding. And as you heard FDA's looking for really creative way of identifying the lowest effective dose and mitigate any potential class effect, toxicity concerns. At the same time, [indiscernible] in such a way so they can look carefully in evaluation of survival assessment [indiscernible] way, not primary endpoint. So there are several implications [indiscernible] driving our development doesn't change it in aggressive way as we were on the way of a number of discussions in exactly the same line, how we bring the highest level of efficacy of our well-engineered profile of our assets. And 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. And that's exactly what we are doing at this point. We'll be engaging with FDA most probably very soon and actually respond to ongoing discussions. So 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. Yes. I was just going to -- I think this is a very timely advisory meeting because [indiscernible] at the moment, basically looking to move into a registration study. And so this [indiscernible] provided certainly additional advice or guideline to industry basically. So I think soon it's very timely. And hopefully, we -- as Marek said, we are formulating our plans and we'll engage with the U.S. FDA to get alignment. Secondly, we are quite confident about [indiscernible] safety profile. And it's a compound designed to improve safety profile to reduce toxicities, particularly liver and GI toxicities associated with the first-generation compounds. So the data we have generated so far seem to be quite favorable. So we are quite confident. Anyways, but this -- the bar has been raised by the FDA. And I think it's good that we have an opportunity to demonstrate fully that [indiscernible]. Anyways, we'll work with the FDA and finalize our plan and move forward with it.

[Operator Instructions] 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?

No. Obviously, this -- it's disappointing news to us, but we are fully committed to bring surufatinib to patients. And we are confident surufatinib has a unique MOA, and the data to date demonstrate its clear clinical benefit to patients. And we will 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. Yes, thank you. Thank you for your participation. This concludes the conference. Goodbye.

Bye-bye.