Okay. Okay, I think we've got everybody. So welcome, everybody, to the 2017 Full Year Results Presentation for Chi-Med, for Hutchison China MediTech. What I'm going to try and do is take you through the presentation quickly maybe in the next 30 or 40 minutes, and then leave ample time at the end of the presentation for questions, for Q&A. You'll see that from this presentation, it's really an update. I mean, obviously, the 2017 results are broadly explained. But each of the clinical trial programs, it's an update. So I'll take you through the changes since the interim results six months ago. So overall, the momentum continuing to build strongly for Chi-Med. We've - we had a fantastic 2017 pretty much by all metrics in the context of the performance of our business as well as the progress of our clinical drug candidates. The first NDA submission went in, in June of last year. We've been navigating the approval process over the last six months. We'd hope it would go faster, but it's a laborious and very detailed process that I'll give you a bit more of an update on later. But we still expect probably around the middle of this year should be done, but subject to SFDA activity and actions on their part. In the context of what's going on at the moment, we're now into or just entering the final stage of inspections, and that's around our good manufacturing practice formulation facilities as well as the GMP facilities, where we produced our APIs. So - and all the clinical reviews have been done, all the clinical site visits and inspections have been done, all of that work has been done. It's now the final part, which is the manufacturing part, which we spent the last three…

Susie Jana, Edison. Good to see the development program for savolitinib in non-small cell lung cancer, but can you just make a little bit clearer now with so many different lines, what the sort of regulatory plan is? Should we expect submission of second line first? Just a bit of detail on that. And on 523, I know that the FDA has requested some additional data. Could just give us some information on the nature of that data? And the last question is on the Commercial Platform business. That 10% to 15% net income growth is - show positive, and obviously, the top line has been distorted with a few things. But should we expect similar top line growth rates if we take away all those impact as a historic? And where - how long do you think, if fruquintinib does launch mid to Q3 this year, how long will it take for sales to ramp up in China?

Great. Thanks, Susie. There are all sorts of questions, I have to remember them.

I'll remind you if you forget.

So the first question is - it was non-small - it was - what's the regulatory plan on savolitinib. So to finalize Phase III pivotal registration studies, you need to go to the FDA and talk to them. You have to have year dose fully understood and laid out and agreed. That work is kind of underway right now. I expect, as we say in our document, that those regulatory discussions will probably be around the end of this year, maybe even early next year. But AstraZeneca is being very aggressive. They're building this randomized, chemo-doublet controlled study, which is powered to be large enough to support ORR and PFS statistical powering. We're doing that now. We're setting that up now. So that all gets led up to sort of the back end of this year when that can start. Hopefully, by that time, we've got the dose figured out. We can go to the regulatory authorities with everything, and then it can be converted from a Phase II to registration study. But that's to be determined. So that's the plan on second line. Now third line is, it requires the same information, the same dose information. So third line, post Tagrisso failure, that information on dosing that plays out over this year will be used to set the strategy for registration in third line. The plan is fully to go ahead in third line. It's just - we're not being as aggressive as we are in second line because, a, the signal is stronger in second line. You've got sort of 60% response rate in T790M-negative MET-positive patients on that combination. So very aggressive there. On the third line, it will come, it's just going to come probably 6 to 9 months later. So that's the strategy, is you just go hard on both of those. The Iressa combination, as I've said, we're talking about China and savolitinib-Iressa combination, and that plays out this year as well. So I think that by the end of this year, we will have started the chemo-doublet global study. We will have figured out, is it the weight-based algorithm 600 for the heavier patients and a lower dose for lighter patients, is that our dose? Or are we going with 300 milligrams for everybody? That's the question. We'll go with one of those. We know that, worst-case scenario, 600 with the weight-based algorithm is going to give you something in the sort of 20%, around maybe 20%, 25% discontinuation rate, which isn't bad considering everything I've showed you today. So that plays out this year. First line, we're also working on that, and that will become more clear in as time goes by. We have quite an aggressive plan on first line. Okay, so does that answer your first question? Second question was, remind me?

It was on the Syk inhibitor, what's the nature of the additional information that the FDA has requested?

Oh, okay. So when we submitted our IND last year on the Syk inhibitor, the FDA asked us to go off and do three months tox testing on the M1 metabolite of the Syk inhibitor. So as 523 has metabolized, somewhere between 20% and 30% of the metabolites that come off of 523 is a single metabolite. And so that's quite a big number, 20% to 30% of the metabolites being a single substance. So they said, look, have you got tox data on that? And we said, No. And they asked us to go back and run a three-month tox on it. So that three months tox is complete. The data is just about ready to be resubmitted to the U.S. FDA, there's no problems with it. We expect the Syk inhibitor and the IND to be cleared, hopefully, before the middle of the year. That's that. And then the last one?

Just on the Commercial Platform, the top line sales and also just trying to put that in context that if you do launch fruquintinib this year, fingers crossed, how many years it might take to ramp up? Obviously, it's in the whole franchise.

So, yes. Okay. So Commercial Platform, the biggest problem with our Commercial Platform is that we don't consolidate the sales of our joint ventures, right, which are growing rapidly. And they're now, this year, $480 million or so, $470 million in sales. So we don't book those. What we book is the sales of our 51%-held Sinopharm joint venture, Hutchison Sinopharm, which is affected by the Two-Invoice policy this year. So there's a sort of a drop-off in sales, albeit no impact on the profit, right? I think once you take this step-off, because of the Two-Invoice policy, then you just sort of keep going at what we've seen in the past, I think in last couple of years, we've sort of said 10% to 15% growth top line and bottom line on our Commercial Platform is what we expect. I mean, this year, the profit growth was 25% as we freed up, built all these new capacity and suddenly realized we've actually been pretty significantly capacity-constrained these past few years. But I expect on the Commercial side core business to just keep growing at 10% to 15%. I think that's conservative. I think we can do better than that. In the context of fruquintinib, it's still going to be quite interesting because where - actually, where the Two-Invoice policy hurts us on Seroquel, it actually helps us on fruquintinib because we're the manufacturer. So actually, Eli Lilly will not be able to book the sales of fruquintinib, we will, as the manufacturer, despite the fact that it's their commercial team that's detailing it. It's a bit messed up, but it is what it is. So as soon as we launch fruquintinib, we'll start to be able to report some of the sales or most of the sales on fruquintinib.…

Yes. Just to refresh - since I'm probably a little bit out of the loop, just on the Lilly fruquintinib. Where are they ex China now?

Yes. So when the FALUCA study reports top line results in Q4 of this year, that triggers Lilly's last option window, which is a two-month window. So just assume we report the results of the FALUCA study. I don't know whether it'll be this stable, but say it's October 1, then they have all of October, all of November to decide do they want to exercise the global option and take the global rights. Now a few things are happening during that two months. First of all, they're really studying the lung cancer data in the context of the FRESCO study, the third-line colorectal data, really looking at efficacy of fruquintinib, number one. But they're also taking into account the differentiation of fruquintinib in the context of Cyramza, their VEGFR 2 antibody, which is a pretty big drug for them globally. But they've developed and they spent an awful lot of money developing Cyramza globally. So they've got some things to think about once they've got that lung cancer data. If they do decide to exercise the global option two months later, then they'll start a four-month period of negotiation of the global development plan. Because they have to put forward full diligence, full commercially reasonable effort in developing fruquintinib globally if the exercise that option. And so that four-month period of agreeing what the global development plan is, is actually really important because we may not agree on the global development plan. We may say actually that's not enough, you've got to go harder. And then they say, Oh, actually, that's what we can do. So that's how it plays out, two months for them to decide if they want it, then enter into four months of negotiation around what's the development plan going to be. If we do agree with the development plan, then it gets done and then they take the global right. And so that's the status basically, okay?

Christian Glennie with Stifel. Just a bit more of sort of perspective and context, I guess, in terms of the dosing and - particularly on savo and the combination. Just in terms of whether this is something particularly new and obviously get the point about flex dosing and things. But just something in terms of where it's come from in terms of your conversation with Astra, is it through regulators? And also, your level of confidence. And obviously, as you potentially step down on weight dose, you don't start to lose some efficacy from the drug.

Yes. This is very common in putting together your global registration plans, dose - and obviously, you have to have the efficacy, first and foremost. If you've got no efficacy, there's no point in discussing dosage, right? Clearly, savolitinib and Tagrisso is a highly potent combination that delivers great benefit to a patient population that today has nothing, right? So that's sorted on response as well as the indications that I've given on duration of response and PFS, this is - put it aside. So now it comes to saying, okay, do you want savolitinib to be $1 billion drug or do you want it to be a $4 billion drug? Well, for it to be a $1 billion drug, charge ahead with 600 milligrams QD, and you're going to have 30% of patients who's going to fall off the combination because of whatever reason. Better, if you want patients to stay on it longer is to fine-tune that dose regimen and bring that number down. Now you can see Sutent, with 36% discontinuation rate, is $1 billion monotherapy, right? But these days, I think to be competitive with the broad range of therapies that are now available, not in this particular indication, you have to doing better than Sutent did 15 years ago. So for us, it's a normal process for Astra. It's a normal process of really understanding the data that's come out of the proof-of-concept studies and fine-tuning the registration trial strategy based on that data. Now you've got to also remember, what we presented in October of last year was preliminary data, so patients continued on these regimen and we've continued to observe these patients. So you have more information as you go. But as I said earlier, I think this is - we're all really encouraged. Actually, the word in the announcement encouraged by this data was not written by us, it was written by AstraZeneca. They are very encouraged by the savolitinib-Tagrisso combination. And it is squarely in their strategic area of focus, and we're moving as rapidly as we can. It's an exciting program. So I think fine-tuning the dose in parallel with getting ready to start this global randomized chemo-doublet study that will be powered to get us to what we believe today, subject to FDA discussion to confirm that, but we believe this will be enough to get us to where we need to go, and that's all happening in parallel at the moment. So it's exciting for us I think.

I just wanted to follow up because, obviously, things are moving at a good pace in terms of 523, 689 will be coming in to the clinic and some of the earlier-stage stuff. Cash is strong at the moment, but are you looking to partner these in the near term? Or will you continue to invest? With R&D going up to $110 million to $120 million, it's going to go pretty quickly. So a little bit of guidance on partnering would be great.

Well, yes, R&D is going up to $110 million, $120 million. But you got the China business generating a lot of cash. You've got partners giving us a lot of cash as well. So the net loss for next year is $19 million to $52 million, right, somewhere in there. It'll probably end up in the $40 million somewhere, I imagine, maybe the high 40s. So the cash we've got at the moment is plenty to see us through next year and well into the year. Probably 2020, I would imagine. I think on partnering, we're in no hurry. We're actually in discussions on a bunch of stuff with regards to the Syk inhibitor, mainly in the context of combinations and kind of nonexclusive collaborations to look at how that compound does with other interesting compounds in the field of hematological cancer. So it's about building a data set, a proof-of-concept data set. I think once we've built that up to being a deep data set, it will be an extremely valuable asset. Looking around, you've got Gilead, you've got to Takeda, they're the only two other players of note working on Syk. They're moving quite quickly, so we have to move quickly, too. But I think Syk, over the next 12, 24 months as our data set emerges, we will be seen as really the only unpartnered Syk inhibitor that's far along. And so I think we would be high potential for big partners coming and looking to collaborate with us. But we want to be in a strong position with a strong data set to be able to then decide if that's what we want to do or do it ourselves. We can decide later.

Just taking the view if Lilly - just going back to fruquintinib, if Lilly doesn't take the program, what's your global plans for fruquintinib?

We're charging ahead. We're charging ahead. And actually, deep down, I kind of hope they don't because what we've got is - the deal that Lilly has, if they exercise the option, is a deal that we did back five years ago, when we were a much smaller company and it's actually quite a good deal. I think one of the reasons that they wouldn't do it is because of the conflict with Cyramza. It's not because it's not a good deal, it's a great deal that they would get. So it's more that conflict with Cyramza. And also, they'd have to be on the line for a massive global development plan, which would be a big investment for them on the back of having just done the same thing for Cyramza. And if there's an overlap, it maybe doesn't make any sense. So we are moving ahead as if they will not exercise their global option. So the Phase I bridging study already started at the end of last year. We expect that by the time the FALUCA study reports, that will be complete, will be Phase II ready. Actually, we may even decide to identify some innovative combinations. That's really what we're most interested, is fruquintinib in combination with other targeted therapies like savolitinib, for example. Fruquintinib and savolitinib in clear cell - or renal cell carcinoma, in our view, is a very exciting combination. It has great potential in combination. So we might get to a point where late this year, we see Lilly is not going to exercise, we finish our Phase I bridging study and we're ready to just get quite aggressive in some combinations. And that leads to another thing that we are doing at the moment, which is starting to build up our clinical regulatory organization in the United States. We've - historically, we've run all global development under our control from China working with CROs and third parties around the world, we've concluded now that we actually have to put our organization on the ground in the U.S. to be in readiness for this. So as sulfatinib goes into Phase II, as fruquintinib starts to potentially get into some interesting global development and U.S. development, we want people on the ground to run that for us.