Okay. Thank you. This is Christian Hogg, CEO of HUTCHMED. And today we welcome everybody to this 2020, Fiscal Year 2020 Results and Business Update Presentation. On the line I also Dr. Wei-guo Su, our Chief Scientific Officer and Head of Research & Development; I have Johnny Cheng, our Chief Financial Officer; and I have Dr. Marek Kania, our Chief Medical Officer in the U.S. and Head of our International Operations. What I'm planning to do today is, given this is an hour long session is spend about 30 minutes, 25 to 30 minutes on the presentation. I'll go through it relatively quickly, as it's all fairly well laid out in our announcement that's just been out for an hour or so, and then I'll leave the second half of the hour for Q&A. And that's an opportunity for the broader team that we have here to answer any questions that that you might have.

Thank you, management. We'll now begin our question-and-answer session. . Our first question is Louise Chen from Cantor.

Hi, congratulations on all the progress this year. And thanks for taking my questions. I've got a few questions here. First question is, could you give more color on how you get to the $110 million to the $130 million, that's obviously a big step-up from 2020. How much do you have in there for potential savolitinib milestones and then maybe more color around ELUNATE and SULANDA? Second question is on the HMPL-689, obviously, making some good progress here. Can you talk about where you think your competitive advantage is here? And where you would fit into the treatment paradigm if this makes it to the market? And the last question I had is how do you plan to build a globally competitive franchise here in the U.S.? Where do you plan to distinguish yourself? Thank you.

Okay, thanks, Louise. So the $110 million to $130 million, you just have to look at what we're doing on for fruquintinib at the moment in the first couple of months of the year, like I said, probably over $20 million in the first quarter. That should bring fruquintinib up, easily up to sort of $75 million, $80 million as a relatively straightforward target. Now we're booking consolidated revenues about between 70% and 80% of all sales, based on the structure of the contract we have with Lilly. So if you're doing 75%, 80% on fruquintinib, you're probably booking close to $60 million in -- $55 million, $60 million in fruquintinib consolidated revenues. On SULANDA it's very early. But we expect somewhere in the sort of $35 million range give or take for SULANDA. But as I say, it's very early, but that our commercial team is confident of that. Then you get to savolitinib, well savolitinib on approval, you're going to receive a US$25 million first sale milestone it’s non-approval, it's actually first sale so that that would be a significant piece of this revenue. And then in terms of the royalties that we'll receive, we receive a 30% royalty on all savolitinib sales in China. And I would expect that would be material, I won't put a number on it at this stage of the game, but it would be material for the year. In addition to all of that, we have a couple of other sources of revenue in oncology. One is the service fees that we earned from AstraZeneca and Lilly for running all various operations and research and development or development operations in China as well as manufacturing on savolitinib as well, that'll be further revenue for us. So because we're responsible for manufacturing savolitinib as well as the MAH holder. So you add that all up, I think, fairly conservatively we will be in this $110 million to $130 range. Then moving on to 689, I'll leave that to Wei-guo to talk about competitive advantage, you have 689 relative to the sort of the current treatment paradigm. Wei-guo, if you'd like to answer that?

Sure. Thanks, Christian. I think between dose escalation and dose expansion in China, we've now dosed over 120 patients, outside China. Marek’s team is also enrolling patients as well. So altogether, we probably have 140, 150 patients now for 689. And we are very encouraged by the emerging efficacy and safety data with this compound. We're seeing really good efficacy in several subtypes of non-Hodgkins Lymphoma. And we actually plan to move into registration intense studies in China first, but perhaps will be followed by the international or global development as well. So not only actually a more indolent subtitle, but also we are seeing some interesting activities in some of the more aggressive subtypes as well. So we’re wrapping up -- we probably will wrap up the China dose expansion cohorts this year and look to publish some of the data from there on. And more importantly, we want to focus on the registration intense studies and hope to bring 689 to registration in the near future. So, yes, we're looking at quite a few subtypes and we're seeing very exciting data there. Some of it’s already published that is dose escalation portion, already published. And if you look at dose escalation, right across all doses, all subtypes, well all was about 50% and with a very interesting different safety profile comparing to some of the competitive compounds.

Great, thank you, Wei-guo. Maybe Marek you could take a crack at the third part of Louise's question, how do we establish a global competitive franchise basically?

Yes, thank you, Louise. This is Marek. So good question. Obviously, broad question. I would say this way, our success will be led by obviously continue building on our foundation of our deep and large portfolio and the success we build in the wake of discovery for development efforts in China. Obviously, our priority first is to address some of the most high unmet medical needs, through our late-stage assets, our single-agent registration strategies, obviously going to build our foundational portfolio. But obviously, as Christian described, our strategy is building our combination efforts and driving innovation across multiple assets, right now we have five and soon to be seven active programs in clinical development. That is the way we're doing this. We're also building high capability and highly talented team of very seasoned individuals across BRAC and science drug developers as well as the very strong commercial team led by Tom Held. So, this will be ongoing journey. But if you're looking for common theme, how we're doing this, we're really targeting high unmet medical needs. And we're truly looking for this meaningful difference for patients. And I think, if anything can be testimony, what kind of science investigators, academic centers are collaborating with us, in the United States, U.S., Europe, and Japan. I think it's also kind of common sense what reflections on this science and molecules external experts have. So it's very encouraging. Obviously, it's the beginning of the journey for International Development. But we've made tremendous progress within next 12 to 24 months in the world to be in a very advanced registration of faith across at least couple of assets. But as Wei-guo said, our lymphoma development with PI3K-delta are very complex and crowded market, but there's still high unmet medical needs on our portfolio, and our profile will definitely distinguish itself. Obviously has worked for everyone, but we're extremely encouraged.

Great. Thanks, Marek.

Our next question is from Ethan Ding from Morgan Stanley.

Hi. Can you hear me?

Hi, yes, can Ethan.

Hi, hi, thank you, Christian for taking our question and congratulations on such a solid year. I would like to ask two questions on perhaps. First, could you just provide some color on the pricing for surufatinib and upcoming savolitinib in China? Maybe compare with competing products if there's any. Also both, I think both surufatinib and savolitinib will be eligible for reimbursement negotiation this year. ELUNATE will be up for renegotiation. Could you remind us about your strategies for these drugs? What kind of price cuts can we expect? That's the first question. And second question; could you provide some rough guidance about your R&D expenses and cash burn, total cash burn in 2021? Thank you.

Okay, great. Thanks, Ethan. So yes, obviously pricing strategies, obviously very sensitive. But we've launched surufatinib pricing at a level that is similar to that of -- that we launched fruquintinib at. So it's up in the high US$3,000, say US$3,800 a month, we're implementing an important means tested patient access program, that enables patients who are paying out of pocket to get access to surufatinib. And obviously now over the balance of this year, we'll be engaging on surufatinib with the regulatory authorities to work to get surufatinib on to the NRDL early next year. So I can't really go into any more detail than that other than to say, similar levels of pricing to fruquintinib give or take. And we will try to make fruquintinib accessible to patients during the period that we have to spend, negotiate and get on the NRDL. Savolitinib, is a bit different, savolitinib has been interesting one, because we're obviously very keen to try to get savolitinib approved in the first half of this year in order that we can then engage in the NRDL discussions over the second half to get savolitinib on the NRDL at the beginning of 2022, right. So, it's a big change a year, two years ago, we would have been get approved in the middle of the year, you're looking to get on the NRDL 18 months later. Now the Chinese regulatory authorities have moved so aggressively, that if you get approved in the middle of the year, there's a chance to get on in six months. So we're working on Savo. I think the pricing benchmark for savolitinib that you should use is probably TAGRISSO, sort of global pricing and China pricing strategy on TAGRISSO that was executed by AstraZeneca that is all public information. I think you won't go too far wrong looking at that as a reference. Finally, on ELUNATE, obviously we get into the renegotiation to renew our reimbursement on ELUNATE. And we'll work with the regulatory authorities on that. I mean, one of the benefits of Eli Lilly kind of getting off to a relatively slow start is that we have generally the discounts are bigger for drugs that have built very large franchises in a short period of time, because Lilly has such a small commercial team working on fruquintinib, obviously that's changed now and we're going more aggressively. But I think we'll be in a reasonably good position to discuss and renegotiate the ELUNATE pricing. I would hope that the discount wouldn't be wouldn't be too significant. So that's really -- that's as much as I can say on that, Ethan. Sorry, the R&D. Well the guide on the R&D spend. Maybe Johnny, you'd like to give a guide on the amount of R&D spending this year?

Yes, okay. So appropriately, we haven't given out a clear guidance on R&D spending but doing of our spending in 2020, I think we'll ramp-up the R&D spending likely to be close to double of 2020.

Yes, that's a fair assessment. I think what you're going to see is, you're going to see China stepping up materially from this $111 million level that we saw in 2020, just because Wei-guo and the team are working so hard to initiate so many -- up to eight to 10 registration studies over the back of this year in China. And so that will be a pretty significant step-up. And then Marek and the International Organization burned around $63 million last year. But the FRESCO-2 study is kicking into full steam over the back of this year. And the expansion of the organization as well as development of multiple assets, I could imagine that could easily double this year, potentially more. So yes, those are the kind of numbers we're looking at.

Our next question is Alec Stranahan from Bank of America.

Hey, guys, thanks for taking my questions and wanted to also offer my congratulations on all the progress in 2020. First on ELUNATE what would you say has made the biggest difference in the increased up tick following the transition from ELUNATE and I guess how much of this year-over-year benefit is coming from NRDL inclusion versus greater efficiencies in the launch? And then I'd be curious to hear your views on the expanding presence of PD-1s from BeiGene, Innovent and others outside of China whether you see any clear leaders among the Chinese PD-1s and I guess how you think this may ultimately play in your go-to-market strategy for ELUNATE, Suru, and Savo given the various combo studies ongoing?

Thanks, Alec. Yes, so maybe I'll answer the first one and on the PD-1 side, maybe I'll ask Wei-guo to answer that. But on what's the biggest difference on the commercial progress of ELUNATE since we took over. While the NRDL -- the NRDL kicked in for ELUNATE on January 1, 2020. So Eli Lilly had three quarters with reimbursement on ELUNATE. And as you can see from our presentation, the sales increase, end-market sales increase for those three quarters last year, relative to the year before was 37%, which I would classify as fairly tepid. Then, our team took over in Q4, and we saw terrific growth. I mean the difference, the real difference was coverage. You go from 120, maybe 140 commercial people across China marketing ELUNATE to 420 plus and growing. By the end of this year, we'll have 600 people on the ground in China covering everywhere, very aggressively. I think the other thing that that does for you is it allows you to get the hospital listings. What's most important, the big benefit of getting on the NRDL is that you can get access to the hospital pharmacies. If you're not on the NRDL, it's very hard to get listed in the hospital pharmacies in China. So you're dependent on retail pharmacies, in the sort of proximity of hospitals. But getting on the hospital pharmacies is the key. And so in the last quarter of last year, we increased the hospital listings by over 40% relative to what had gone on before. So having a bigger team, better coverage and that translating into more aggressive hospital listing activities, we believe it was up to about 290 hospital listings at the end of last year, and that hopefully will double over this year. So that will make a big difference, I think. So those are the key differences relative towards broad coverage, and a real focus on getting hospital listings. Wei-guo, maybe you could comment on how you see the PD-1 landscape playing out and how we fit in with that both in China and outside of China.

So I'm not sure if the question was about clear leader PD-1 compound on the China market or just in terms of sales or revenue or you're talking about -- asking about the difference in efficacy and safety. So I mean I can't comment on market size. But in terms of different PD-1s that we've been working with we've been working with -- we're working with TUOYI, TYVYT, and also Genor's PD-1. Obviously we've not done any head-to-head comparisons to compare the different PD-1s but we don't have a lot of data to make any conclusions, reduce the different safety profiles, obviously that's quite, quite normal, consistent with the PD-1 single agent, safety profile. The only thing may be relevant in terms of efficacy, it's the fruquintinib in combination with TYVYT, Innovent and also fruquintinib in combination with Genor's PD-1 in the same patient population in late-stage, advanced stage CRC the data will be published at the upcoming ASCO. So, you may be able to make some comparison there. But bottom line is that we're seeing similar data there whether it's driven by PD-1 or driven by fruquintinib, it's hard to tell at this point. But the top-line data in terms of efficacy appear to be similar and the data will be available at ASCO. So I think in general VGFR in combination with checkpoint PD-1 or PD-L1 I think this obviously already a lot of data available and a clear evidence of synergy as well. It's really about for us anyway to zoning of landscape in China, and also outside China, how indications we think we can take advantage of particularly in terms of differentiated VGFR compounds, as I said in PD-1s are quite similar. But VGFR compounds are quite different in terms of for instance of vandetanib versus regorafenib versus cabozantinib and now we have fruquintinib and surufatinib clear difference in efficacy and safety. So, we're building a very large database through our basket style Phase II study for instance surufatinib in combination with TUOYI, fruquintinib in combination with TYVYT and we have seen quite really encouraging emerging data. And obviously, we will examine against for instance the Pembro fruquintinib combo, where in terms of safety and efficacy profile, and we'll select certain indications to move forward with. So we basically, we're very early in the Phase II, as I mentioned, the Basket study is data emerging really quite encouraged, and the world will need to wait a bit to, for the data to mature and we're quite optimistic that we'll move forward with some of the indications that we're seeing with a very encouraging data. And these can be both in China and outside as well. Sorry, I can't comment on Whampoa.

Wei-guo, you currently answered just from the international development perspective. Christian shown on the slide, we have also, as you know there are active collaboration with BeiGene and tislelizumab and so actually combination found is starting across fruquintinib and surufatinib across multiple cohorts, which will be obviously building on the signals we have across multiple partnerships that with this specific late-stage development PD-1 in U.S. with large presence, BeiGene has in U.S. that's going to be very fruitful collaboration, leading to potential great signal.

Next question is for Paul Choi from Goldman Sachs.

Thank you very much, Christian. Let me also offer my congratulations on all the progress in 2020. A couple of clinical questions from us and then maybe just one strategy question. Just from the combination of surufatinib plus BeiGene and tislelizumab can you remind us is there any reason that the recommended Phase II dose wouldn't be 250 milligrams given your prior experience in prior work with the Junshi PD-1?

Maybe I'll leave that to Wei-guo, Wei-guo and Marek to comment. I don't think that should be any difference but unless I'm missing something.

Yes, I can make a comment. As I mentioned, I don't see a lot difference in terms of efficacy, but safety profiles can be quite different. For instance, I mentioned fruquintinib in combination with TYVYT and also fruquintinib in combination with Genor's PD-1 and the recommended Phase II doses for fruquintinib are different. So whether --

Sorry I'm asking on surufatinib?

Yes, I know. So whether surufatinib in combination with tislelizumab will be 250, I don't know it may be 300 who knows? But I assume it is too far from far from 250. So, it's quite difficult to tell at this point. For instance, you probably saw, I'm not sure if we published that, but it should be published fairly soon at the ASCO that fruquintinib recommended dose regimen is different between TYVYT combo and also Genor's PD-1 combo. So I think as I say the different PD-1s, in terms of efficacy this was a mechanism of action, very similar, but safety profile can be quite different. And depending on the small molecule tox profile, whether there's any overlap or not. So it can be, I think it's quite conceivable, it can be quite different actually.

And Paul, we'll answer this very quickly as part of the standard design, you have the escalation phase, also simplified safe delivery which exactly we will answer this question in our ongoing studies.

Great, okay. Very helpful, thank you. And then on the 689 registrational trout, can you maybe provide any sort of preliminary feedback or guidance that you received from the USFDA with regard to the trial population? And do you think the 13 mg dose that you identified at ASH last year would also be the dose used for that study?

Maybe I'll let -- I'll let -- well, I think the question is with regarding our U.S. strategies that what you're saying, Paul.

Yes.

So maybe Marek, you can go ahead.

Thank you. Thank you, Paul. So just to clarify, Christian says we’re preparing discussions with the USFDA. So as of today, we're obviously still in the final stages of escalation. While we see very encouraging profile, including a very encouraging activity in escalation phase of the U.S. study, obviously we'll lead this to conclusion of that phase. Now, as Christian described, our quite large population of China Study and our emerging data from U.S. will lead us to that discussion with USFDA. So it's still to be completed in the second part of this year. But we’re very encouraged by signals we see in our China Study and as well as the U.S. escalation phase. As you know, we'll definitely build on our past practice that U.S. regulatory is totally open for considering data generated in China or elsewhere, as long as, as I've said, obviously high unmet medical needs and bring innovation, and we've done this through surufatinib in pre-NDA discussions as well. We'll take the similar approach of open and transparent discussion with USFDA, looking at the data in this clinical setting. So stay tuned on this.

Thanks, Marek.

Okay. Thank you.

To your second part, hang on Paul, second part of your question was, do we expect those similar correct to China published data. We're nearing completion of escalation we're right now at 25 milligrams and so far, so good. And so, if you're asking me to speculate, I expect growth will be in a similar range, we still not be approaching 30 milligram cohorts which will complete within a couple of months or less, depending on the DBLP observation method. So I expect that those will be highly likely to think.

Okay. And then one strategy question which is with regard to capital allocation Christian, how you're thinking about balancing that across your clinical programs, building out your commercial footprints. And when in your mind does this, does the oncology business become self-sustaining? Thank you.

Thanks, Paul. Yes, I mean we're in a mode right now, where we're just moving aggressively, as aggressively as we can to maximize or realize the value of our assets, both inside and outside of China. Obviously, we're being very choiceful on the indications that we're moving into registration studies. We're not moving everything but the proof of concept data that that's being developed PD-1 combo, whether it be 689, 523, et cetera is compelling. So, as we said earlier, as far as the burn, it'll probably double on the R&D side over this year, relative to last year. And that's a level of burn that is manageable for the company at this stage. So I'm not resource constrained at this point. On the commercial side, I'm just seeing such terrific execution from our China commercial team. I think we're not anywhere near a point of diminishing returns. So, the concept of building our team from 420, up to 600 by the end of this year is only going to deliver in a material incremental value to the company. So, I think we're in this phase of our evolution of a company where we're accelerating, I think we need to keep a close eye on the equity capital markets. I've mentioned from a strategic standpoint, in this announcement that we continue to evaluate and observe equity capital markets in the context of potential Asian listing, so Hong Kong or a Shanghai listing. So I think from a financial standpoint, we're in a good position in that we have the resources to push everything as hard as we can certainly for the next 12 to 24 months. And I think the value we'll create for the company during that time will really be material. So hopefully that answers your question.

Next question is John Newman, Canaccord Genuity.

Hi, team. Thanks for taking my question and also, congrats on the progress in 2020. I think you guys must be working in your sleep around the clock a whole lot going on which is excellent. Just had two questions. The first one is, I've always been very excited about what you're doing with surufatinib in the U.S. with the NET filing, which is at the NDA excuse me with the FDA? Just curious if you could give us an update as to how that submission is proceeding and if you would expect that that could be an accelerated approval. And then the second question I had is just on the SAVANNAH study with AstraZeneca. Christian, it sounded like you were reasonably confident that the optimal Phase III dose might emerge in 2021. And I just wanted to ask about that? Thanks.

Thanks, John. I'll do the SAVANNAH first and then I'll hand it over to Marek to talk about how the NET NDA is going in the U.S. and priority review et cetera. So on SAVANNAH, yes, that study is a great study. It's enrolled a lot of patients. We -- as I said earlier, we've completed the enrollment of the 300 milligram QD dose in combo with 80 milligrams TAGRISSO QD. And now we're enrolling the 300 milligrams BID, as well as the 600 -- beefing up our 600 milligram QD data. It's just a really well run global study. We are -- I'm confident that by come mid-year maybe early Q3 we'll -- we and AstraZeneca will have a very clear view on the biomarker strategy, the dosing strategy, the dose regimen strategy, as well as the line of treatment that is most relevant is it going to be everybody, is it just going to be off the first line TAGRISSO failure, off the second and third line TAGRISSO failure, so all of that's playing out, is playing out well. And it just takes time. And, but I think we're well ahead of the competition, and we'll be in a good position. So, hopefully that answers the question. Maybe I'll hand it to Marek to talk about U.S. NDA rolling submission for Suru.

Sure, thank you. So, submission is afforded in a high intensity mode. We're under Fast Track designation. Therefore, for rolling submission, we submitted first wave, end of December and we should be completing our NDA submission with Wave 2 and 3 by end of likely April. Just to clarify, we're not -- our strategy is not accelerated approval, which would be based on the surrogate endpoint and then the requiring complementary standard. We are within full approval strategy. So, obviously, it would be up to FDA to design type of review, which will happen within validation period after completion of submission, last wave of submission modules. So FDA has 60 days to validate and send you a letter assigning the type of review. So obviously, open questioning this will be priority review or normal review time. It's to be seen honestly, based on the FDA decision. So we're very excited, how it's working, our team is working very hard, but it's progressing on track. As you know, it's time that we feel good about it.

Next question is Tony Ren, CLSA.

Hey, yes, thank you for taking my question, and again, congratulations on the solid progress. Just the two quick ones from me. The first one is just a clarification, perhaps Christian, you can take this one about the R&D expenditure in 2021. I think I heard you said the international portion right the $63 million is going to double. So is the China portion, the $112 million, is that going to double as well in 2021? That's the first question. And then the second question is about your Savo, so obviously, you guys had a good readout from SAVANNAH study. But that's at ASCO GU; we also had the SWAG 1500 study in PRCC, in which it didn't do too well. How do you guys make sense of the results from these two studies? Thanks.

Okay, sure. Thanks, Tony. Good questions. So on the R&D spend, yes, I think U.S. could double, if not more than double. I think China from $111 million investment in 2020; I don't believe it'll double but I think it'll, may be 50% increase. That's more likely the outcome on the R&D. The study you mentioned from ASCO GU, that was the Pap MET study, right, Pap MET study that study Cabozantinib, sunitinib, savolitinib and Zubrod, somebody else right. But that wasn't a biomarker, a biomarker selected study. So that was basically all PRCC patients. So you don't expect a MET inhibitor to do well in a patient that is not MET positive. And as we know, in papillary renal cell carcinoma, the proportion of patients that are MET-driven is roughly 40%, give or take. So you had 60% of the patients there in that study that were never going to respond to a MET inhibitor. And, in the field of renal cell carcinoma, VGFR inhibitors are obviously in clear cell renal cell carcinoma, they've been a standard of care for many years and still are in combination with the PD-1s. But and so you would expect the VGFR inhibitors to do Cabozantinib, for example, in this case to do better in PRCC relative to the broader PRCC patient population on biomarkers selected than you would expect for savolitinib. But I would imagine, if you do a retrospective biomarker analysis on that study, identify the MET positive patients, savolitinib would no doubt be the superior treatment.

And our last question is Rajan Sharma from Deutsche Bank.

Hi, thanks. Thanks for the question. I was just hoping that you could kind of give us your perspective on recent developments in the EGFR non-small cell lung cancer space, particularly kind of three asset and J&J’s Bispecific and just potentially how savolitinib fits within that and perhaps how it compares it in the context and also whether you see any kind of potential negative impact on your ability to kind of recruit into future Savo trials and in non-small cell lung cancer space, given the competitive dynamic now?

Sure. Maybe I'll ask Wei-guo to answer that question.

Yes. So J&J’s Bispecific, they're now in the first line, basically non-small cell lung cancer. And so I don't think we will compete directly with them, not only in the first line, but also they're not really selecting for the MET status. So we'll be really biomarker driven and with a very clear patient selection strategy. So in terms of clinical trial enrollment competition, I don't think we're in the same patient population, but in terms of in the future, when we're talking about market competition, I think we will be very different products, obviously we're oral, and they are IV. And for first-line patients, who have years to live, we think oral would offer a very good advantage in terms of convenience, and also compliance as well. So that's our belief. And we actually talked to some of the KOLs in China. There are obviously a lot of EGFR mutant, non-small cell lung cancer patients in China. And a lot of them were quite skeptical about first-line IV products for many, many years. So obviously, efficacy is number one. We're all in same boat at this point, getting -- just getting started in the Phase III. So we'll see in terms of efficacy, I think if both remedies are efficacious, then it comes down to patient population and how these treatments will be delivered.

Okay. Does that answer your question?

Yes, yes, it's helpful. Thanks.

Great. Thanks, Rajan.

And this is the end of the Q&A session and apologies for the one who still queue up on the audio and the web. And I'll now pass the time to Christian and the management for the wrap up. Thank you.

Okay. Well, thanks very much, everybody for taking the time to join the call today. Yes, just to finish it off on a very positive note. I think 2021 will continue to be just a really important year for the company. We're making great progress, I think as you can hear from Wei-guo as well as Marek and the presentation. So thank you very much all for your support. And we look forward to kind of continued dialogue as the year goes by. I think it'll be one where we will have a lot to talk about. So thanks very much everybody and take care.

This is the end of the conference. You may disconnect now. Goodbye.