Hutchison China MediTech Ltd at Bank of America Merrill Lynch Healthcare Conference

May 16, 2018 PM UTC 查看原文
HCM.L - Hutchison China MediTech Ltd
Hutchison China MediTech Ltd at Bank of America Merrill Lynch Healthcare Conference
May 16, 2018 / 08:00PM GMT 

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Corporate Participants
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   *  Christian Hogg
      Hutchison China MediTech Limited - CEO & Executive Director

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Conference Call Participants
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   *  Ying Huang
      BofA Merrill Lynch, Research Division - Director in Equity Research

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Presentation
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 Ying Huang,  BofA Merrill Lynch, Research Division - Director in Equity Research   [1]
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 My name is Ying Huang. I'm the senior analyst covering U.S. biotech here at Bank of America Merrill Lynch. We're very pleased to have our next presenting company, Hutchison China Meditech. And we have the CEO, Christian Hogg with us. So Christian will have a few prepared remarks, and then we'll go into a fireside chat format for Q&A. Christian, thanks for coming to Vegas.

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 Christian Hogg,  Hutchison China MediTech Limited - CEO & Executive Director   [2]
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 Great. So thank you, Ying, and thanks everyone for coming. I'm going to just cover some very high-level slides on Chi-Med, where we are at the moment, the stages of our operations and our clinical programs and, as Ying Huang said, we'll have some questions.

 So on a high level, where we are at the moment? The pipeline has moved very rapidly over the last couple of years. We are -- you can see the 2 circled items at the top there are probably the most important things that are going on in our pipeline at the moment. The first is our fruquintinib NDA was submitted in China for third line colorectal cancer last June. We've been working really hard as a company to navigate the NDA process with the Chinese FDA. We've been learning our way. It's our first NDA in China. It's a complex process, but it's getting close. We're currently in the sort of the final stages of the inspections on the GMP certification of our new formulation facility. That's the last major step of the NDA process. So we're hoping to complete all of that over the next probably month to 6 weeks. And then, we will -- there's some analytical work that needs to be done on the products that's produced during the GMP process and then we go into kind of waiting mode for approval hopefully.

 The second big thing was the -- and then launch later this year hopefully for fruquintinib. Second big thing is savolitinib. We intend to start our global studies, the combination with Tagrisso-savolitinib in second line non-small cell lung cancer. Those will kick off, those global randomized studies which will become registration studies, later this year. We're running 6 Phase III studies at the moment on multiple drug candidates and you can see 22 different proof-of-concept studies that are underway. A total of 36 studies we're running at the moment. So the discovery engine is -- continues to produce. We've just nominated a candidate for regulatory talks. I won't go into the details of what target it's against, but what you're going to start seeing from us over the next 3 to 5 years is some increasingly interesting sort of second-generation I/O targets that we've created, we're working on and that will be used in combination with our existing 8 clinical drug candidates.

 And the commercial organization continues to move rapidly. 2,300 medical reps across China now, very large commercial organization, generating a lot of cash, which we're putting all into progression of our clinical drug candidates. This chart is way too busy, but it shows the level of development that we are undergoing at the moment on our key candidates. So savolitinib, the selective c-MET inhibitor is in 14 different clinical studies at the moment. Phase III in papillary renal cell carcinoma globally. We're going to start the Phase IIIs in non-small cell lung cancer this year. But many Phase IIs underway in gastric, in lung, in prostate, all c-MET-driven patient populations. And fruquintinib, 3 phase IIIs enrolling. The second big Phase III readout that will follow the -- hopefully, the approval on colorectal cancer, will be third line non-small cell lung cancer. That reads out -- that Phase III 527 patients study reads out in December of this year, likely December. The gastric cancer Phase III in second line is enrolling quickly. And the 2 Phase IIIs on savolitinib in pancreatic neuroendocrine tumors and also extra pancreatic met patients are moving now, what we believe towards completion of enrollment sometime very early next year. So those studies have been slow, but they're getting there, they're getting there.

 High level, the Syk inhibitor is moving nicely. We've got expansion studies in Australia and China on the Syk inhibitor that are moving. We hope that at ASH we'll have something to show if the data is robust or big enough, the data set is big enough. The PI3K-delta inhibitor, very clean PI3K program. We're going through Phase I dose escalation at the moment, but we're very excited about what we're seeing there. And the FGFR inhibitor is moving in Australia and Canada in parallel. And we're also excited about what we're seeing there.

 So it's been 18 years of effort to put this pipeline together and to get it to where it is. It's been over USD 500 million that's been invested in this to get where we are today. We're on the brink of our first approval, which is a major milestone for the company. And we're extremely excited about what's to follow.

 So this is a high-level chart talking about the main sort of 8 to 10 shots of pivotal success. Six of them are enrolling at the moment. The other 4 intend to start enrollment in the coming 6 to 9 months. So it's a very deep, late-stage portfolio of activities we have. Savolitinib is particularly exciting, given the Breakthrough Therapy designation sort of target that we have. I think, the efficacy that we saw in the Phase II study we presented at World Conference on Lung Cancer, where we saw 60% response in MET-driven second line non-small cell lung cancer. We feel that, that's a level of efficacy that should allow for us to ultimately go talk to the FDA about Breakthrough Therapy designation and accelerated approval. But we'll see when we have those discussions with the FDA.

 I'm extremely excited about the Tagrisso combination. It is -- Tagrisso is obviously a therapy that's doing extremely well. And MET activation as a resistance pathway in EGFR mutation-positive non-small cell lung cancer is an extremely important resistance pathway. And so we are well positioned with AstraZeneca as our partner to take full advantage of this.

 Maybe, Ying, since we've got 15 minutes to go, should we leave it there and start the Q&A now? Or would you like me to take them -- everybody through the -- each drug candidate briefly?

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 Ying Huang,  BofA Merrill Lynch, Research Division - Director in Equity Research   [3]
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 No, I think we may have the Q&A.

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 Christian Hogg,  Hutchison China MediTech Limited - CEO & Executive Director   [4]
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 Okay, great.

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Questions and Answers
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 Ying Huang,  BofA Merrill Lynch, Research Division - Director in Equity Research   [1]
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 Thanks, Christian for that introduction. So maybe first question is you're getting close to the finish line for fruquintinib in China. Can you give us a short update on where things are for that approval and what's the time line here? What remains to be done here before the state drug administration approve the drug?

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 Christian Hogg,  Hutchison China MediTech Limited - CEO & Executive Director   [2]
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 Thanks. So as I said in the brief presentation there, the process of NDA approval in China is extremely complex and disciplined. I think we've been really amazed at the depths to which the SFDA goes in their inspections. It's being eye opening. It's the first NDA that we submitted, and it's the -- it's been a learning experience, I have to say the least. So the major -- the major -- the 3 major areas of work on an NDA, number one is, all the preclinical tox work, validating that, inspecting it, inspecting the sites in which we did all our preclinical tox work and ensuring that it was all done to GLP standard. That's the first step. And it's done in series. So once you get past that step, it's checked. You move into the clinical data and statistical inspections and analysis. And in that process, the FDA -- the China FDA send -- we ran our study, the Phase III study in 28 sites across China. So they pick 4 or 5 of the key sites and send in their inspectors into those sites to inspect GCP compliance and every aspect of those programs. They go very, very deep into individual patients, all the way down to lab, lab data and process of collecting the lab data, ensuring it is reliable. That GCP in the clinical part of the NDA process was completed and signed off on early this year. And that now lead us into the third and final stage, which is the GMP certification of our newly built formulation facility, and the GMP compliance and certification of our API manufacturer. We used a contract API manufacturer. That work is happening today in China. The inspector, CFTA inspectors are there in our facilities and will continue to visit and inspect over a period of the next 3 or 4 weeks as we produce from API all the way through finished product. That should complete in the middle of June sometime, at which point the product of that GMP inspection will be sent for analysis. And analytical work will be done on the product to ensure it meets spec, it meets specification. That should be complete probably sometime in July. At which point, hoping that everything goes well, at that point, it should all be complete. And at that point, it's a matter of just waiting for approval. So could it be an approval in August, September, October? I don't know, it will really depend. But we should be completed with the whole process by sometime around the end of July.

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 Ying Huang,  BofA Merrill Lynch, Research Division - Director in Equity Research   [3]
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 Because Lilly will be responsible for the filing effort, what part are you playing as an organization? Are you trying to get ready for some sort of a co-promotion? Or what kind of commercial effort would you put in?

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 Christian Hogg,  Hutchison China MediTech Limited - CEO & Executive Director   [4]
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 So we're working really closely with Lilly on this. The fruquintinib launch is the first major launch for Lilly in China in a decade. So it's a really important initiative for them and they're putting a lot of resource against it. Obviously, Chi-Med has a very deep commercial organization in China, and you can see it from our work on Seroquel, for example, as well as our own products, over 2,300 reps across China covering almost 100,000 physicians in China. So we kind of stand ready to help Lilly in any way we can. I mean, Lilly, contractually has invested a lot of money for the right to commercialize fruquintinib in China, and that's their right. But they are -- they remain open to dialogue around how Chi-Med can help, maybe in secondary provinces, if they're not covering those provinces as deeply as we can, maybe we can help there. But this is an area of ongoing discussion and we'll see where it leads. But I do know this, Eli Lilly is taking their responsibility extremely seriously and getting ready for a really important launch.

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 Ying Huang,  BofA Merrill Lynch, Research Division - Director in Equity Research   [5]
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 How would you frame the commercial opportunity for fruquintinib in this line of colorectal market in China? And then secondly, is it critical for you to obtain the so-called reimbursement on the national drug list for the commercial potential to be realized?

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 Christian Hogg,  Hutchison China MediTech Limited - CEO & Executive Director   [6]
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 Got it. So colorectal cancer in China is a huge problem. You've got around 400,000 new colorectal cancer patients a year in China. By the time they get through 2 lines of chemo into the third line setting, you've probably got 50,000 or 60,000 patients a year, which is a big unmet medical need today in China. Based on the median PFS of fruquintinib of about 3.7 months, you're talking -- and penetration into that patient -- untreated patient population maybe of 20%, to the point where you get to peak sales. You're talking about a peak sales opportunity maybe, for third line colorectal, something in the region of USD 110 million to USD 160 million a year. So it's a relatively small, but it's an important indication to get the drug approved, and allow us to get into the market and then bring fruquintinib into early line treatment through life cycle indications. I think that what's going to be very interesting is the other 2 Phase IIIs that are enrolling at the moment, third line non-small cell lung cancer and second line gastric. Second line gastric is the big market potential. You've got about 200,000, 250,000 second line gastric cancer patients a year in China. It's an enormous unmet medical need. So for us, hopefully, we're going to get the approval on third line colorectal cancer some time later this year. Shortly thereafter, by the end of this year, we'll have the top line results of the Phase III in third line non-small cell lung cancer, so I think that will come in around Q4, maybe around December. If that's positive, then you're going to see some real momentum on fruquintinib. The approval, a positive readout in non-small cell lung cancer and -- I think we'll see momentum build there.

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 Ying Huang,  BofA Merrill Lynch, Research Division - Director in Equity Research   [7]
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 So as you mentioned, Christian, there is a third line non-small cell lung cancer trial that's ongoing here. What kind of data should we expect here that will be considered meaningful and useful in the Chinese market because as we all stand, the way we treat cancer or lung cancer specifically is a little different from what we're using in the States here?

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 Christian Hogg,  Hutchison China MediTech Limited - CEO & Executive Director   [8]
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 Yes. So I think in the -- the standard of care in China in non-small cell lung cancer is quite different from the U.S. You've got 50% to 60% of patients in China are EGFR mutation-positive non-small cell lung cancer, that's 3x or 4x what you see in the U.S., which is more like 10% to 15%. So you're getting a lot of patients treated. Now with the EGFR inhibitor off patent, you're going to see a lot of patients treated with EGFR inhibitors in China. But that still leaves -- and so that will be the first line of treatment. They'll fail on that ultimately and then they'll go on to the chemo doublet probably or Tagrisso if they can afford it and they're T790M positive. So I think that the opportunity in non-small cell lung cancer is pretty significant and the standard of care is quite different. But I think fruquintinib in third line non-small cell lung cancer, it is a tricky area. Third line non-small cell lung cancer patients are quite erratic in their disease progression. They can -- they can look like they're doing very well on a drug and then they fail very quickly. So -- but we're optimistic about fruquintinib in this setting. The phase II data was very positive, although it was powered only for PFS. We saw a 3.7-month median PFS versus placebo or the standard of care or the control arm was only 1 month. So that was very compelling PoC result. I would -- to answer your question directly, Ying, what's the scale of benefit we would hope for, something similar to what we saw in colorectal cancer. I think in that third line setting in lung, median OS is probably something like 6 months. If you're able to see 8 to 9 months median OS on fruquintinib that, I think, would be a really meaningful benefit to patients.

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 Ying Huang,  BofA Merrill Lynch, Research Division - Director in Equity Research   [9]
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 All right. That's clear. So that's a good lead to savolitinib in lung cancer you and your partner, AstraZeneca, are running some trials. And recently, we have seen some encouraging response rate of savolitinib in later line non-small cell lung cancer. So in this case, in later lines, in your opinion, what kind of PFS are you trying to achieve here before you can push forward into later trials?

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 Christian Hogg,  Hutchison China MediTech Limited - CEO & Executive Director   [10]
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 So the Phase II data we presented at the World Conference on Lung Cancer is very interesting dataset. It was c-MET driven, basically all comers, post first generation EGFR TKI failure. So the rest are the Tarceva failure. So what you saw in those patients were some patients just came straight off of Iressa on to the Tagrisso-savolitinib combination. That's our target patient population. These are very -- basically pretty healthy patients that have gone through a year-or-so of treatment on Iressa or Tarceva. Their tumors have been in control. They have progressed, but they still oftentimes are working and living a normal life. We saw with those patients very strong PFS. we haven't published it, but a level of PFS that we're very comfortable progressing forward with. However, in the Phase II study we also had, because of it was all comers, you had some patients that have been on 4, 5, 6 lines of therapy. They're MET-positive, but really sick patients. So the encouraging thing is you see 60% response, no matter what line of treatment these patients come to you at. But the PFS is different. If it's a true target patient right off of Iressa or Tagrisso, they do very well and the PFS is very encouraging. If it's a patient that's been on 6 lines of therapy and they go on to savolitinib-Tagrisso, their PFS will be shorter by nature of the fact they're much further along in their disease. So I can't give any numbers as to the months. I know you want me to, but I can't give any numbers as to the number of months of PFS that we see and that we would expect to see. We'll present that at a scientific conference in the future. But needless to say, Astra has made the decision to move into global studies on the savolitinib-Tagrisso combination. Those studies should start enrolling in August, September of this year. And I'd say, we are confident that the PFS benefit and the OS benefit will be really material for patients in that target patient population, those that just come off of first generation EGFR TKIs.

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 Ying Huang,  BofA Merrill Lynch, Research Division - Director in Equity Research   [11]
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 Is it fair to assume that you might have data presented at ESMO in October this year?

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 Christian Hogg,  Hutchison China MediTech Limited - CEO & Executive Director   [12]
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 I would expect we could, we could. But that's still to be determined.

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 Ying Huang,  BofA Merrill Lynch, Research Division - Director in Equity Research   [13]
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 And then you have a Phase II/III study for Tagrisso in combination with savolitinib in second line c-MET-positive and T790M-negative patients. Can you talk about the dosing strategy for savolitinib? And then what's the plan to move that combination into a potentially registration study?

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 Christian Hogg,  Hutchison China MediTech Limited - CEO & Executive Director   [14]
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 So we have -- we're still working on 2 doses. We are comfortable, and AstraZeneca is comfortable, that either of the doses is fine for the global registration study. The dose that was used in the Phase II was 600-milligram q.d. daily dose -- single daily dose. It was well-tolerated. In combination with Tagrisso, you've now got 2 very active highly selective targeted therapies, tyrosine kinases inhibitors. The level of those dose discontinuation due to AEs was something in the -- around 30%, which is a level that's quite common for even first generation monotherapy TKIs. So we're happy with that. We are expecting that we will go with what we are in the Phase III in papillary renal cell carcinoma, which is actually a weight-based algorithm. So 600 milligrams for patients over a certain weight, probably 50, 55 kilos, and maybe 400 milligrams q.d. for patients under that weight. We think that, that will be more tolerable, and you're covering the target fully 24 hours a day with that kind of regimen. So that's the sort of base plan. We're also though, currently, enrolling a second study, a supplemental study of 300 milligrams q.d. dose. Just because, we know that 300 milligrams q.d., you're also covering the target 100% 24 hours a day. And we're looking to see -- we expect response will be strong and the impact on PFS shouldn't be significant, but we don't know that for sure. So we're enrolling that study at the moment and we'll see. If the 300 milligrams q.d. dose looks really good in terms of ORR, in terms of PFS similar to the 600 milligrams, then we'll go with 300 milligrams in the global registration study. If it doesn't, for whatever reason, it's futile relative to 600 milligrams, then we'll drop that and we'll just go with the 600 milligrams weight-based algorithm.

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 Ying Huang,  BofA Merrill Lynch, Research Division - Director in Equity Research   [15]
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 Can you talk about the safety findings from the PRCC renal cancer study compared to safety findings from the lung cancer study? I presume there might be some difference because you're using a combination regimen in lung cancer, so therefore, there could be an overlapping toxicity here between those 2 drugs.

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 Christian Hogg,  Hutchison China MediTech Limited - CEO & Executive Director   [16]
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 So that's the big difference. So for the monotherapy, savolitinib in papillary renal cell carcinoma, a really well-tolerated drug. I mean, you -- drug candidate. You've got literally discontinuations due to AEs somewhere in the region of 8% -- 8% to 10%. It's very low. The primary AEs that emerged in the savolitinib monotherapy are nausea, fatigue. So nothing really material, and we were very encouraged by this. It was a very well-tolerated monotherapy, savolitinib. In combination with Tagrisso, you obviously got -- you've got 2 very active drugs on top of each other, and you do tend to see some Tagrisso-based AEs emerging, rash, et cetera. And in combination, the combination, particularly for really week patients, very late-stage patients, can be challenging from a toleration standpoint. But broadly speaking, it's a very well-tolerated combination. So nothing that we are that concerned about. Although, we -- as we've just mentioned, we continue to work on dosing regimens to see if we can optimize it. Because if we can get dose continuations due to AEs down from the sort of 30% level down into the 20s or into the -teens, then you talk about the drug combination has a much broader market potential and -- potential for usage basically.

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 Ying Huang,  BofA Merrill Lynch, Research Division - Director in Equity Research   [17]
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 So maybe now we can talk about some of these, at least currently, still wholly own programs you have, such as the Syk program. What's the near-term milestone for those programs? And given what you have done with savolitinib and fruquintinib, once you have proof-of-concept data for those compounds, do you plan to partner or you want to keep development by yourself.

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 Christian Hogg,  Hutchison China MediTech Limited - CEO & Executive Director   [18]
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 So the Syk inhibitor is moving rapidly in parallel in Australia and in China. We're through Phase I dose escalation. We're now into expansion, expanding into more sites in both Australia and in China. And I would say, it's picking up really good momentum. We, obviously, having treated many dozens of patients, are seeing the kind of signals that we want to see -- that we would hope to see and are working to broaden our dataset as quickly as we can. I think we'd hope that maybe later this year or early next year, we'd be able to present some data on the Syk inhibitor. I think the -- obviously, hematological malignancies is the main focus for us at the moment, but we're also, we remain interested in immunology as well. I think as far as partnering is concerned, it's not our top priority. Our top priority is broadening the data set. I think once we get through proof-of-concept in hematological malignancies as well as perhaps start off a proof-of-concept study in immunology on the Syk inhibitor, then we're much better positioned to discuss potential partnering. But it's not our top priority at the moment. Our top priority is to move these programs. We have the financial resource and the organizational resource at the moment to do this.

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 Ying Huang,  BofA Merrill Lynch, Research Division - Director in Equity Research   [19]
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 And then maybe we have time for last question. Besides the programs we've talked about, including the Syk inhibitor, what other programs are you excited about in your pipeline?

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 Christian Hogg,  Hutchison China MediTech Limited - CEO & Executive Director   [20]
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 Okay. Well, that's a loaded question. I'd say, we are particularly excited about the PI3K-delta at the moment. It's still in early development, but we are seeing some really interesting efficacy playing out on the PI3K-delta. It's the cleanest PI3K-delta TKI that we see out in the market. It's the most potent. Likely, the recommended Phase II dose or the effective dose will be somewhere in the sort of 5 milligrams q.d. dose level. So very, very powerful PI3K-delta compound with great PK. And so we're extremely excited about that and seeing how that develops. I think our FGFR inhibitor, selective -- FGFR has been a difficult target for the industry, but the understanding on the translational side is really -- has come a long way. And we're able to see relatively early on in patients that we expect to respond well to our FGFR inhibitor, we're seeing some exciting early efficacy evolving. So -- emerging rather. So these are the 2 sort of quiet ones that I would say are coming behind, everything that's in late development that we're pretty excited about.

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 Ying Huang,  BofA Merrill Lynch, Research Division - Director in Equity Research   [21]
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 Great. Thank you, again.

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 Christian Hogg,  Hutchison China MediTech Limited - CEO & Executive Director   [22]
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 Thanks.




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