Has expanded quite significantly too, right? Because if you look at the previous drugs, you know, the PFS is much shorter and now it is longer. So we continue to see not just, you know, gaining a healthy market share, but also seeing like more colorectal cancer. Maybe previously they were just using recycled chemotherapy in the third, third line scenario, but they are, they are now using, you know, the more innovative drugs. So we continue to be quite positive on that one. Okay, great. If memory serves, you got a $400 million upfront from your partner, Takeda, which I believe ranked in the top ten of licensing upfronts last year for that arrangement. So I guess the question here is, you know, you got a very large milestone, but based on your ongoing partnership with Takeda, you know, how do you think about the role of the partnership model for future launches in the U.S., you know, particularly, you know, in oncology, right? You know, what are the key considerations here versus going alone? Yeah. So I think, you know, Takeda has really set up a very good, collaboration, so I think we are very collaborative. I, I think really utilizing MNC for the product launch and commercialization is really taking, advantage of their strength, in the global marketing, which HUTCHMED doesn't have, right? So from the... You know, at least I was, at ASCO last week. We see a very strong enthusiasm in the marketplace about the, FRUZAQLA. And the physicians, Takeda put on a good show. There are also education centers are talking about fruquintinib, talking about the global data. We see a large penetration of the, you know, the- their MSL team, their, the commercial team, really have a very good, excitement generated. Even their booth, the whole screen, looking at the product launch, is actually quite unique and very eye-catching, just from my perspective. And so I think we have set up a very good example for commercialization, with the global partner and really helping us to leverage the R&D manufacturer and the China experience, right? So, and the other example, we are also taking our second product as the MET inhibitor, savolitinib, is also have a early-stage partnership with AstraZeneca. We think this really set us up, you know, in a good foundation, to really leverage their strengths to not only but the future global development, taking on the further investment for that. As you also mentioned, thinking about, we think also is a de-risk approach for commercialization. Probably sometimes realizing the China-based geopolitical risk to some for the short term, we think this is the our licensing and partnership will be our approach for the global commercialization. Sure. I want to circle back towards geopolitical risks, maybe a little bit towards the end, but stick with fruquintinib for now in terms of China, where you've done really well commercially. Particularly since, you know, taking reworking the rights that you previously had with Eli Lilly there in terms of the commercial. So can you maybe talk a little bit about where you could go beyond in terms of CRC in terms of potential label expansion, and, you know, how do you size up key opportunities? I think first and foremost probably is the gastric opportunity there in China. Yeah. Thank you, Paul. Yeah. So, we are very excited about the gastric cancer opportunity. It's a huge patient population in the second-line setting. So the trial we have conducted is a China Phase III trial, fruquintinib plus paclitaxel versus paclitaxel. You know, the data was actually reported earlier this year at the ASCO Plenary. And, you know, last week at the ASCO Plenary, provide an update the data with the oral presentation, and it's also have a concurrent publication in Nature Medicine. We are very excited about the data. Not only show very robust, you know, it's a dual primary endpoint with the progression-free survival and overall survival. For PFS side, we see significant improvement of the progression-free survival, almost doubled with the hazard ratio of 0.57. Also we see a very robust response rate, 42% at the treatment arm versus placebo for 20%. The overall survival also we have seen pretty much along all the second-line data, 9.6 months overall survival. Is this the longest OS benefit we have seen for the second-line gastric cancer treat? We also published the, you know, post-therapy treatment imbalance lead to the, you know, significant difference of the imbalance of the post-treatment lead to the OS doesn't really achieve the clinical, I mean, statistical significance. But still, we see the benefit. So we are very excited about the data. So the data is already supplied the analysis to the CDE. We expect the decision Q3 this year. So this will be an important area with high unmet need. The other area is the combination, because I mentioned specificity of the fruquintinib against MEK receptor. It is a very good partner with other immunotherapy, chemotherapy, like what we see in the FRUTIGA therapy. So the next one, we also present our pivotal Phase II data, fruquintinib plus sintilimab in second-line endometrial cancer. We observe very robust overall response rate. So OS, overall response rate, 35% in this treatment setting. And we also submit the NDA. This is the clinical trial design was already agreed upon with the CDE. We submitted the application, NDA was accepted in April. We expected that decision by end of this year. Along the other label expansion, so we also see a combination with the sintilimab combination PD-1 in the renal cancer. So this is the second line versus axitinib or everolimus. The patients were I mean, recruitment was completed last year. We are waiting for the event later this year. It is event-driven, so hopefully, if the data is positive, we're going to file NDA next year. So that will really further expand the label for fruquintinib in China. A lot of these data also kind of, we're in discussion with partner to see if there are any global opportunity for fruquintinib in a global setting to further maximize the value for fruquintinib. Can you just remind me, in China, second-line standard of care in renal is still axitinib. Is axitinib. Is that correct? Yes. Yeah. Okay. Yeah, in Other markets, there's PD-1 plus Right. cabozantinib or PD-1 plus other No immunotherapy combination has been approved in China. Okay. That's why we agreed upon with this clinical trial design, with the CDE. Yeah. Okay, very good. I want to maybe pivot to savolitinib in lung, where your partner, AstraZeneca, obviously has a very large, you know, blockbuster EGF franchise with their TAGRISSO drug. And you know, you and your partner have indicated that you're planning to potentially file an NDA by year-end based on the SAVANNAH data in a second line study, which is global, not just China-based, and that could come by year-end. Can you maybe remind us, first of all, how much of the MET-positive population in second-line lung this could potentially address? And we can start with that. Yes. So, you know, just, on top of that, I think savolitinib was actually approved in China, in a very specific indication in the MET, MET exon 14 mutated patient. So, you know, in the approved indication, you know, in the U.S., I we know that capmatinib, tepotinib also are approved, in METex14, but it's actually is very representing a small patient population because METex14 is a key driver mutation in non-small cell lung cancer, but it's only account about 1%-2% of patient population. So it's a relatively small, kind of a market. And for the global development plan, AZ and HUTCHMED is taking is the addressing the MET, aberration, right? Overexpression, the amplification, that really account for a strong, resistance to VEGF TKI. So in the global setting, in the Western patient population, MET, EGFR, MET mutation, EGFR mutation is actually quite large, account for 10%-15% of the patient population. In the Asian patient, it's just much higher. It's about 40%. The Asian patients have EGFR-driven mutation, so that lead to non-small cell lung cancer. So sooner or later, even though you have first generation, second generation, third generation EGFR TKI, but regardless, the patient eventually progress from those EGFR TKIs. So one of the major mechanism for EGFR is the MET amplification or overexpression. That, you know, from the previous Savanna trial we published, is account about over 30% the patient population. So that actually addressing a even larger patient population. So the SAVANNAH trial is really taking this approach. In the second-line EGFR mutated resistant patient population, the combo with savolitinib and the TAGRISSO really significant extend the PFS and had a higher response rate. So the overall response rate from the previous, you know, the exploratory stage, the SAVANNAH trial, we published it about 50%, so 52% overall response rate. And that really lead to the development for this SAVANNAH trial to really addressing this patient population. So if the data holds, right, the primary endpoint is overall response rate. It reproduce the previous result, AstraZeneca is going to lead the NDA submission later this year. That's, you know, our partner's timeline, and we really hope that will also, you know, after the FRUZAQLA, it put our HUTCHMED innovation to the global stage the second time. We're very excited about this opportunity. Yeah. Okay, great. You mentioned this earlier, that sales of like Pemazyre and other MET drugs, you know, only address a small part of the market, and sales of the approved inhibitors, while small, you know, haven't quite hit blockbuster status yet. So how do you think you and AstraZeneca maybe can grow the market here? So sort of, is a lack of information among clinicians? Is it just poor treatment options, poor patient behavior? What sort of factors can grow the market? Yes. Here in the MET space? Right. So actually, you know, I think that's really under, you know, the MET amplification, EGFR resistance is really the kind of a not yet precedent-setting data before. But, you know, even though it was through AstraZeneca development and our development, I think people are realizing the MET amplification is an important resistance mechanism, but there's just really AZ and HUTCHMED is really in the early pack of lead in this indication. So certainly the physician education, certainly the additional data, you know, I think hopefully the publication coming out from this study, Savolitinib Pivotal Trial, will really further awareness, set us apart from other competition in this field. And even for the MET exon 14 mutated patient, we also a t HUTCHMED, we have this China registration trial before. We also have a line expansion indication. So we already completed not only the second, third line, which is already approved indication in MET exon 14 in China, we also have our first line readout published earlier this year at the ELCC, which has also set us apart from the other competitor in the first line setting. You know, we have observed very long, you know, high response rate, over 60% ORR in the first line, MET exon 14 mutated patients, and also the overall, I mean, the overall survival has now been reached, the PFS, about 13 months. So it's really significant in MET-driven disease area. So we already submit the, the first line, if label expansion in China. Hopefully will also come approval next year, early next year. Because of that data, we also have a full approval in the second, third line setting and the first-line setting. So that will certainly grow the market, not only for the MET exon 14 mutation, but also the EGFR resistant, you know, non-small cell lung cancer setting. Yeah. Great. I want to switch gears and maybe talk about what I think is your most exciting but maybe least known asset, which is sovleplenib in ITP. You've recently presented some data on it, and you have more data coming up here at EHA, but I think the data are really impressive. You know, when you think about standard of care here is largely steroid treatment and things like that. And your durable response looks to be pretty long as well, too. So can you maybe help us contextualize the data, what this means in the disease area of ITP and what next steps for the program are? Yeah. Yeah, thank you, Paul. This is, you know, this is more exciting data. We're actually presenting the data on Friday, at EHA in Madrid. So the abstract has had an early release, but the funny thing is, Paul, the EHA still informs us that data has a kind of a, you know, at an embargo stage, but the abstract is all. That's what we can talk about, is absolutely, you know, fascinating as what you point out, because the duration of response for this, in this heavily pretreated, ITP patient population. Because, the traditional - I mean, the trial was conducted, in patients. It's 188 patients, 2-to-1 randomization, ESLIM-01, Phase III trial in China. And we have observed overall response rate of 48%. So our initial Phase I proof of concept study was about 40% ORR, but this, the Phase III data is even far exceed our expectation, with the durable over- overall response rate, which is the primary endpoint, and the placebo is zero. So that really spell out how clean, how robust the data will be. Just give you a context, the SYK inhibitor, which is in the U.S. and EU, there's approved the medication, is a fostamatinib in a similar second-line setting, it with a less TPO-RA pretreated patient. So, in this setting, the TPO, TPO-RA is the primary second line. After steroid, TPO, TPO-RA are primary, the second-line setting. So for the, the fostamatinib data, even if it go, approved, the overall response rate is 18%. Okay, so same class. What we believe our, not only we have a very specific, Syk inhibition, but also, similar like, like fruquintinib, because the unique and the specific inhibition, you lead not only increased efficacy, but also decreased the undesired, off-target toxicity. So what we fascinated about this data, in the, in this patient population, heavily pretreated, placebo response is zero, right? You see the average prior line of therapy is four lines of therapy... and, seventy-five percent of the patients have been previously treated with TPO or TPO-RA. Some of them have multiple TPO, TPO-RA treatment. And so we're gonna also present the, you know, subgroup analysis, you know, in EHA with the two posters. So, the data really show this compound is clearly highly potent and, you know, it also does not have the prior therapy, which is the other mechanism is TPO-RA. Primary mechanism is stimulate the platelet production to bone marrow. The Syk inhibition is primarily, it has a dual mechanism. One, is the inhibitor macrophage destroy the, the platelet, which is due to the autoantibody, body production. And also they inhibit the B cells, production of anti, antibody production. So these two mechanisms, addressing the fundamental of the, immune thrombocytopenia, it also does not have the, TPO, TPO-RA, has the, more severe toxicity, which is the platelet overshoot and lead to so high thromboembolic event. So we see zero thromboembolic event in the phase 3 data. That's great. Also, we're gonna present the patient-reported outcome, the improvement of physical health, some of these data also at the EHA later this week. Okay. Yeah. Great. I want to turn maybe just to regulatory next steps for the program. Maybe starting with China, where you did complete the Phase III, and maybe just sort of, you know, what happening there, potentially with a priority review or accelerated review there. And then, in terms of the global opportunity for ITP, can you maybe just comment on where you are with regards to alignment with the FDA and other regulatory agencies outside of China on a potential pivotal trial here? Yes. So we communicate and discuss with FDA about the global development plan. So we are already starting international phase one trial to really looking at the dose escalation, dose optimization for this trial. So the design has been agreed, and with FDA, we're already starting this trial. We opened a few centers already in the United States, with the first patient coming, you know, pretty shortly. And internationally, we think, you know, this is really still y ou know, because the compelling data, we have a lot of enthusiasm from investigators in the United States, in EU, Australia, and so the global development will kick in pretty shortly. Also, future, there has huge opportunity, I think, for the global development, not only in the previously pretreated setting, because the safety profile, the unique, the specificity of the Syk inhibito r. You also have a potential to move earlier line, even in the combination setting. So that's what we believe this molecule has a lot of potential because truly has this best-in-class potential for global development. Okay, great. I wanna maybe change tacks one more time and maybe turn to a bit of a sensitive subject, but maybe, David, if you could speak to, you know, what has been, you know, seemingly like a more hostile stance of the U.S. government towards China biotechs and, you know, potential exposure to sensitive technologies. So, can you maybe talk about what strategies, if any, you know, HUTCHMED is taking to navigate this environment, the current environment, and maybe, you know, what you see as either potential headwinds or tailwinds for China biotechs such as HUTCHMED? Sure. I think it's a very, very topical issue last few months and on a lot of investors' mind. I think for HUTCHMED, as you know, we focus on innovative drugs, right? We focus on the science, and I think since day one, we have been aspiring to not just be a China biotech, but, you know, one that can have global commercialization. And, you know, we have to deliver that, right? You know, not just through, you know, partnership and R&D stage, but also the commercialization stage. I think, like, when we did the deal with Takeda, two years ago, right? Almost two years ago, you know, part of it, of course, is for the commercial reason, right? We got huge financial upfront. We got, you know, royalty without a lot of risk. So that's kind of the de-risking part that Mike mentioned. But now, you know, at this stage, there may be another de-risking part that, you know, we do have an MNC, you know, on the label of the bottle, it's Takeda. If you look at the approval labeling, it's Takeda. You know, so that actually may de-risk a little bit, you know, versus we doing it all by ourselves. But the other thing, of course, is, I think at the end of the day, it's still a product which have much more compelling data than some of our competitors. I think that, that truly is what we can control. I mean, like, a lot of the other things like the geopolitical risk or any other legislation that may come, it's not controlled by us, right? You know, we can just go with the flow. But, you know, the thing we can continue to focus on is, you know, we have good drug candidates. I think, as you may have noticed, that, you know, recent days, you have some seen high-profile news about some company not having very good manufacturing standard, right? You know, we are, again, like, we are very proud, that, you know, we pass all the manufacturing inspection, all the clinical site inspection, with relatively, you know, almost no, no issues at all. And I think that is not something easy to say for a lot of our peers. So those, those are the things that we, we continue to focus. Like, I think, you know, I always remind people that we are more than 20-year-old company. You know, we've went through a lot of ups and downs. We went through a lot of the things that takes time to learn the know-how, right? Not just in terms of clinical, but also manufacturing. So we think that this should equip us further down the road, not just for the China market, but also for the global market. There still continue to be this kind of uncertainty, but we focus on what we can do best, right? So, you know, for our next product, next potential U.S. product, you know, savolitinib, we already have our partner in place. For our next, you know, second inhibitor, we definitely will continue to seek out capable partners, multinational, big biotech, to be our commercial collaborators. So I think that's kind of the answer. I think the other thing, of course, is science is still science, right? If you have a drug that can extend the PFS by 50% or 100%, I think that is still much more important than any other geopolitical risk. Okay, great. You're also, like, talking about, you know, pivoting to breakeven and profitability in 2025. I guess, as you think about your product cadence and your OpEx trajectory over the next few years, you know, maybe can you just comment briefly on, you know, how you think you're progressing against that goal to be breakeven or profitable? And then just, you know, how other factors are coming into that. Sure. So at the end of last year, we have very, you know, relatively quite safe balance sheet, you know, over $800 million cash. And, you know, of course, last year was a profitable year because we have the upfront payment from Takeda. This year, we will continue to do our R&D and everything that you know. But then 2025, we target to be breakeven. It's not one-off breakeven, we want to be sustainably growing afterwards. So the burn can be mitigated quite nicely. I think, for not just our major shareholder, but also for, you know, future investor shareholder, I think that is something quite important to see not just good product coming out from our company, but a sustainable operation that can do many other things. I think it's not just the current pipeline that you should be looking at, but you know, with our skill set, with our balance sheet, you know, we can do many more other things, you know, in the medium-term future. And I think that is quite key in an uncertain capital market, as we all know these days. Yeah. So and we do also have a new manufacturing plant recently opened in Shanghai. It's not in full-scale commercial stage yet. You know, in for clinical batch, we can do that. But then, you know, in the next few years, we will enter into the commercial readiness of these manufacturing facilities, which will hopefully also continuously increase our cost synergies, our production margin should gradually increase with this. So that's another part of our thinking, that it's not just at a clinical front or approvals, or regulatory front, that we want to be a commercially sustainable and continuously growing company for our shareholders. Okay, great. Maybe to close, if you could just remind us, Michael, maybe top two or three catalysts we should watch for over the near term- Yeah. From Hutchmed. Yeah. So, yeah, Paul, this, I just kind of a mindset, you know, mentioned. I think the major catalyst will come from our, you know, from R&D side, is really the near-term approval, NDAs, right? So first is the indication expansion for ELUNATE, for fruquintinib. We continue to have the GC, the, you know, MET, the RCC, either at the NDA stage or approval or the NDA submission stage. And also the savolitinib, we're gonna have a full approval for METex14, and our exciting, partnership with AZ will lead to a new indication globally, right, for savolitinib, for the non-small cell lung cancer with the MET EGFR mutant resistant patient population. That's really the indication expansion for all these existing products. The next is the new products, which coming, we mentioned about the Syk inhibitor, not only in the ITP, but also we have development in the lymphoma. We also have other autoimmune disease potential to be developed. The approval for ITP is coming. And also in the EHA, we, we're gonna show our PoC trial for the, you know, warm autoimmune, hemolytic anemia. That's also very robust data. We are very excited about our Syk inhibitor. In China, we also have our in-licensed product, tazemetostat EZH2 inhibitor. We're completing this, NDA filing later this year. Okay. So new product, new indication, it will be the key driver and catalyst for ours to contribute our 2025 commercial breakeven and sustained growth stage. So it's gonna be exciting for the company. Yeah. Great. Okay, we'll have to end it on that note because we're out of time. Thank you very much. Thank you, Paul. Okay. Yeah.