Okay, great. I'm Yigal Nochomovitz. I'm one of the biotech analysts here at Citi. This is a continuation of our newly introduced C-suite series, where we feature management from some of our covered companies for a 1-hour discussion about the pipeline and other topics. It's my great pleasure to have with me this morning Josh Smiley, who is the COO of Zai Lab. Josh started in August of 2022 after a 26-year career at Lilly. As a reminder, if you have questions for me, you can just email me and I'm happy to shoot them over to Josh during the conversation. Josh, welcome. Thank you so much for taking the time to speak with us for 1 hour. I appreciate it. I think a lot of people are familiar with Zai Lab, but I think a lot of people also aren't. I think maybe to start with, if you could just outline the strategic vision for the company over the next, say, 5 or 10 years. How do you see the mission evolving both in the pipeline as well as the commercial side? How do you see the transformation of Zai Lab into a larger company with a greater commercial footprint in the next, say, decade or so? Sure. No, thanks. Thank you all. Thank you for having me. First, the company was founded in 2014, so we've been around for, I guess, nine years now. We've got. In China. Oh, can you hear me? I'm sorry. I think we had some choppiness on the audio. Maybe could you mind saying that again? I'm sorry. We didn't hear you. Sure. Is it okay now? Yes, it's a little better now. Okay. All right. Is that okay? I think so. Hopefully it stays. Yeah. Okay. Yeah. All right. I was saying we've been around for about nine years. We've got headquarters in Shanghai and Cambridge, Massachusetts. Our initial emphasis has been to build a best-in-class portfolio in oncology, immunology, neuroscience and infectious disease. In China, we've got four products on the market. The biggest is ZEJULA for ovarian cancer. We've got eight more products on the way in China. Really what, you know, our initial emphasis has been to partner with western biotechs to bring their innovation into China. If we play out the eight launches, we expect to be commercially profitable this year and profitable on an overall basis by 2025. We will continue to build out our portfolio in China. You should expect to see us continue to bring partnered products in those areas. Particularly now in ways that we can complement the deep expertise we're building in areas like women's cancer, lung cancer, gastric cancer and immunology. We do expect though to also launch innovation in markets outside of Greater China, both through our own internal R&D efforts. Our most advanced project is a topical IL-17 that we're gonna start a global phase 2 program on in psoriasis later this year. We've got discovery efforts in oncology and a few early projects in phase 1. We'll also continue to explore partnerships and business development to bring not just products into China, but to bring best-in-class types of opportunities into the rest of the world. I think when you look at the portfolio that we have in China, it's really exciting. It's gonna, you know, provide a great opportunity to impact, you know, many patients in China and with that to bring, you know, pretty significant economic returns. We don't give like long term guidance yet other than to say we'll be profitable at a bottom line in 2025. I think if you add up some of the opportunities that we'll be launching in the next, you know, two to three years, you know, you clearly see multi-billion dollar potential in China. We'll continue to build on that and I think continue to be seen as sort of the one of the go-to enhance their clinical development on a global base and also to be able to, you know, capitalize on the commercial opportunities in China. So I think hopefully with that, you call it gives a little bit of a overview of who we are and where we're headed. Yeah, no. That's really helpful. I think a lot of people maybe don't appreciate some of the points you made in terms of the profitability for the commercial business by, I think you said the end of this year. Could you just expand on? Yeah. -expand on that a little bit? Are you referring specifically to the ZEJULA franchise or all the four products? Sure. What are some of the assumptions that are built into that statement? Yeah. A lot of people are realizing that that's going to happen. You know, for the full year of 2023 we'll be commercially profitable. If If you look, we've got 4 products, producing, sourcing those products, promoting them to physicians, and that also includes the royalties we pay back to innovators. We also will launch a fifth product this year, efgartigimod, it includes all of the launch of expenses there. Really all of the expenses in China, take out all those expenses, we will be profitable. ZEJULA drives that profitability. It's profitable. It was profitable in 2022. It's our biggest product and has been on the market the longest. You know, I think when we look at, you know, opportunities and profitability in China for the kind of products that we're bringing in and marketing, so in areas like oncology and immunology, we think we can continue to get good pricing. We're marketing these products in a pretty concentrated fashion. Patients in China tend to travel, when they have oncology, travel to tier-three hospitals, so we have pretty concentrated sales and marketing efforts. Similarly for immunology and efgartigimod, we're building about a 100-person sales force to launch that product initially in myasthenia gravis. I think when we look over time, Yigal, at the portfolio that we have, we do expect to have, you know, greater than 50% operating margins in China. For, you know, again, for the reasons I mentioned, best-in-class products that bring good pricing with them, concentrated sales and marketing efforts. You know, then you take that, of course, we have corporate expenses and R&D expenses. By 2025, even as early as 2025, certainly in 2025, we'll be cash flow positive at a bottom line. Of course, then that'll grow significantly over the second half of the decade as we begin to scale the 8 launches that I mentioned upfront. I think relative to how investors may view China on a, you know, sort of product basis or one-off basis, the portfolio that we've built, the approach that we've taken, we think, yields a really, economically attractive, investment opportunity. I think there was a point where, correct me if I'm wrong, but you had provided some very rough... I mean, I don't know if I would use the word guidance... Yeah. Some rough-. Yeah. Sort of numbers around. Yeah. Yeah. Around, what kind of revenue situation, what revenue picture you might achieve for some of the products. I think it was for oncology by, you know, by the end of the decade. Is that something that you could re-reference for everyone, so we understand that? You know, we said early last year that when you look just at the portfolio that we had built in lung and gastric cancer, and ovarian cancer just because of ZEJULA. If you looked at those 3 together, you know, we saw sales potential by the end of the decade of between $2 billion and $3 billion just in that portfolio. We've had, you know, very positive advances, I think in the last year since we said that, most notably, and I'm sure we'll talk about it, you know, progress in Tumor Treating Fields and LUNAR. That would have been not a high probability sales event when we talked about this a year ago. We also have added TIVDAK to the portfolio in women's cancer. I think that was meant to sort of just give it a directional sort of size. I think, though, if you look at everything that we have in the portfolio today in China, and that includes now e fgartigimod, you know, in immunology and all the indications that are under development there and KarXT for schizophrenia. I think it's certainly reasonable. Again, we have to execute. These all have to be approved and everything else. I think when you start to add up the opportunities that, you know, that we're building, I mean, there's certainly a $5 billion type of opportunity long term in China with the portfolio that we have today. Again, that's not meant to be guidance. I think certainly just when you look at the size of the opportunity, the patient numbers in China, and the high probability we have around many of these products, that's not an unreasonable, you know, number to aspire to. Of course, we'll continue to build on that with, you know, other deals and continue to progress our internal pipeline. Okay. No, that makes sense. I think for some of the investors that sort of tangentially know Zai Lab but don't really focus on China too much, it would be super helpful if you could at a sort of high level, just highlight what the differentiation is for Zai Lab's business model and strategy versus some of the other competitors that we all know out there. Some have been around longer, some have been around shorter. HUTCHMED, Junshi, Innovent, Hengrui. There are others, just in a sort of simplified way, if you could clarify, that would be really helpful, 'cause I think a lot of people that don't follow China closely just don't have a good grip on that. Yeah, sure. You know, of those products you I mean, those companies you mentioned, each of them have a sort of, you know, a slightly different, you know, approach or, or angle themselves. I think if I look at Zai Lab, you know, relative to that group collectively, I'd say the biggest differentiator today is the, I think the breadth and depth of our innovative portfolio in China. Again, as I mentioned upfront, oncology, immunology in our sand and other, you know. Yigal, can you hear me now? I think, Josh, you know, it might be helpful if you turn off the video. I'm being told by the technical people that if you turn off your video, it might help with the bandwidth on the audio, if you wouldn't mind. Yeah. Thanks. Okay. Okay. I think, as I say, each of those companies have their own, you know, unique, you know, aspects. I think for us, the breadth and depth of our best in class, first in class portfolio in China, I think is probably the biggest differentiator. You know, we see very good economic opportunities to leverage that portfolio, not just across a few assets, but, you know, a compelling lung cancer portfolio, a compelling gastric cancer portfolio. Really best in class, first in class products that give us then the flexibility on pricing to be able to drive, you know, compelling operating margins and otherwise. You know, we're gonna continue to focus. That's the number one focus that we have is to continue to drive and execute a tremendous portfolio focused in those areas in China. Can you hear me? Yeah, no, this is. Thanks. Okay. Okay, good. Just wanna make sure. All right. I think then as we think, you know, I guess would compare us maybe to Hengrui or something to say, you know, we're not, they've got a very broad portfolio, in some cases innovative opportunities, super competitive, you know, classes. We really want any we're bringing into China's, you know, is really first then is good regulatory processes and good pricing opportunities. I think as we think about our opportunities outside of China then, we're gonna be selective. We do wanna have opportunities, and I mentioned IL-17, but to bring innovation into the U.S. and Europe and other markets. We're gonna be very selective there and continue to, you know, sort of stay in those same therapeutic areas where we think forward, if we think it's got a compelling benefit, to patients. You know, I think for the next number of years, expect that the majority of our sales and profits are gonna come from China. We're gonna be selective about introducing innovation outside the U.S. I think with that, the breadth of that portfolio in China, we have an opportunity to, as I say, be really, make big impacts on patients, but also be really profitable. Yeah. You touched on one of the questions I get often about Zai is just the strategy for in-licensing. I mean, obviously you had, I think it was 2021, if I'm not mistaken, where it was a high watermark. Yes. Eight deals. 8 in 21. Yes. Yeah. Yes. Last year, you know, well, a lot of things happened last year, everyone was faced different types of headwinds. In any case, it was lower. You know, I think you're kinda sticking to your strengths in terms of the known therapeutic areas. What more can you say in terms of the pacing and focus for those licensing deals? It sounds like you're taking a more critical lens maybe than you had in past years. You do have a lot on the plate in terms of assets. Yeah. Just wondering how. Yeah. Thinking about that. Well, I think probably, you know, 2021 was a high watermark, and that's, yeah, I don't think we're gonna repeat that. Just, you know, there just was a great confluence of events and great assets that came together. I think on the other side, 2022 and only doing 1 China-based deal is probably low. I think maybe if you sorta take the 2 years together and say, you know, we probably expect somewhere between 2 and 3 good assets a year to come into China, that's, you know, that's not always gonna happen, but that's a reasonable, you know, sort of expectation, I guess. Maybe, maybe, you know, 2 is probably a place to sort of, you know, over time, sort of hang a marker on. They're gonna be we want them to be generally in areas that are complementary or synergistic with the infrastructure and teams we've built. TIVDAK's a great example because it's in women's cancer. It will fit, you know, right into our ZEJULA sales force and infrastructure, same position, same targets. We'd love to do those kind of deals. I think, you know, if you look in lung cancer, though, we're covering, you know, a huge swath, I think now of opportunities, you know, on the targeted space with adagrasib for T and Ras, you know, ROS1 positive, you know, et cetera. I think, and now with the potential for Tumor Treating Fields. You know, I think we're gonna be selective as we look in lung cancer, and we're gonna want something that's gonna bring something, you know, new and better to patients. I think we will continue. I mean, for the right opportunity, we would move outside of the therapeutic areas we're in, but that opportunity has to be really compelling, right? It has to be big enough to support on a standalone basis the entry into another therapeutic area, and, you know, have some, you know, compelling patient benefits or opportunity to price well and, you know, and so on. I don't, you know, we don't have sort of a particular new therapeutic area we're looking at. We would be opportunistic. I'd say it's a very high bar to do that. You should expect continued deals in China, in oncology, immunology and neuroscience, you know, not more than 2 a year, probably. You know, some years that may be 3 because of just the way deals flow. I think we've built a great reputation. You know, Western companies that are looking for partners in China tend to come to us, and we, you know, can engage and dialogue then. You know, I think that'll continue. I think the 2 areas you should expect some new activity in would be, we have talked about opportunities to partner more broadly with some of the bigger companies, the bigger biopharm companies on maybe more than one asset. Our deals to date have been 1 asset at a time, and of course, you know, many of those assets were working on multiple indications, but they tend to be asset by asset. We think there are, you know, some bigger companies that, you know, we could do a multi-asset deal with and they could, you know, could involve other exchanges of, you know, pipeline assets or portfolio help and could entail a capital investment, you know, from that, from that partner. That's something we're intrigued by and pursuing. I think the 3rd piece then would be, I think we've done a great job historically of picking really good assets and winners and, you know, we can point that capability at doing that for opportunities that aren't just China-specific. We're gonna be very selective there. You know, don't expect a huge number of deals or big acquisitions there or anything, but gone that, you know, investigating, you know, good oncology opportunities, for example, we will look to do this out, you know, in a select basis outside of China. Did you lose me? For a sec, but I got most of it. Okay. Basically, for example, there could be potential for a deal where there's a two-way street where you might license in some portfolio of assets instead of just one. In that exchange, you may out-license some of your internal assets in the same transaction. Is that a fair way to think about it? Because I know. That is. Yeah. Yeah. That is. I think there are, as I say, there are companies that have broader portfolios that, you know, historically have invested in China but may, for some of the areas where we've got deep expertise, think we'd be a good partner and, you know, I think we are, you know, we can be an attractive partner to the bigger biopharmas. Uh-oh. Hello? Yeah. Can you hear me? You just cut out there for a second. Okay. Okay. I think I got the gist of it. In terms of some more specifics, you know, I found this one little graphic on your slide, in the slide deck, very interesting, where you're making the point about having accelerated timelines to approval in China relative to some of the industry norms, for ZEJULA and Optune, less than a year, for unreviewed timelines. Just curious, you know, what's the secret sauce behind beating the standard timelines? What is Zai doing that's making everything more efficient when interacting with the China regulators? Yeah. I think it starts with having great innovation. We make sure as we're partnering that, you know, as part of our due diligence process, of course, we're making sure we understand the data. We're also working with thought leaders and regulators in China to understand how much of a opportunity and unmet need there is and the receptivity to the technology. We have a great regulatory team, and I think that's, you know, we understand the process. We stay current on changes, you know, from a policy perspective or otherwise. I think that, you know, I think we also have now a history of success. If we're committing to a bridging study, you know, if we're having those negotiations, I think regulators, you know, have seen us work across multiple projects and understand that, you know, we're gonna follow through on our commitments and we're gonna bring thoughtful strategies to them in terms of whether it's bridging or otherwise. Again, I'd say, you know, it starts with great products, and that's... We're not gonna compromise on the technology we bring to the Chinese regulators. We've got a great team, and we do have very thoughtful strategies around how to ensure that what we're submitting, whether it's bridging or part of a phase 3 program, that that's been well thought through and well discussed before we get to the, you know, the final stages of the submission. Okay. We'll get into some more details in a little later on the bridging with the Mirati asset and with the KarXT. I just wanted to ask you mentioned pricing power and how to price in China. Obviously, we're gonna get some of the details on the NRDL for QINLOCK and NUZYRA soon. You also make the point in a lot of your corporate materials around this, the commercial supplemental insurance, which appears to be increasingly important, if I understand correctly, for how to think about the payer landscape in China. Why is that so critical? What does that do for Zai Lab to be able to access that? You know, right, today, if we look at supplemental insurance, we see probably about 100 million patients in China are covered. We see that number growing to somewhere between 200 million and 300 million over the next, you know, handful of years. It's a, it's a fast-growing market. It provides, I think a couple things. I think first, you know, in advance of any NRDL listing, it gives the opportunity for physicians to get experience with Product in a meaningful way. obviously it gives access to, you know, to patients more quickly and more broadly than, you know, in the past. I think for a product like Optune, where we have the most and the longest experience, it's, you know, it historically has been the only option for patients to access this kind of innovation because medical devices which Optune, you know, qualifies as, have not been eligible for an NRDL listing. Now we think that's gonna change, and we can talk more about that. Again, I think it's, you know, our view is it's somewhere in the range of 10%-15% of the patients may have access through supplemental insurance. Optune in 2022, was the second most reimbursed product through supplemental insurance, only behind KEYTRUDA. We do have, I think, good experience and good listing capabilities here. I think, you know, I... It is important for the reasons I mentioned, but really I think the innovation we're looking at, ultimately, we want it to be listed, you know, from a national drug list perspective, where we really wanna impact the entire population. For you know, for the kind of drugs we're bringing in, we think they bring significant benefits and can ultimately lead to, you know, a good calculus as it relates to the pricing we get relative to the volume opportunities for patients. Supplemental insurance is a good gives us a good running start in many of those cases. Well, that's interesting. I was gonna ask about QINLOCK and ZEJULA. I know you won't be able to comment specifically on numbers yet because you're probably gonna talk about on the call soon. More conceptually, you know, when you think about the price cut on the NRDL versus the trade-off on the upside on the volume, like, what does that trade-off look like? I mean, is that generally a win when you take the price hit and you can benefit on volume? Like, how has that played out so far? Yeah, yeah. So far for anything, you know, again, we have now experience on three products, ZEJULA, you know, QINLOCK and ZEJULA. I think the, you know, the case has been you get much, you know, the volume picked up relative to the price reduction has been positive and quite positive. I think, you know, just as I can't get into the data yet on, you know, on QINLOCK. I would say that we, you know, we started the negotiation, you know, we went into the negotiation with, I think, pretty close to the maximum price you could have of, you know, like 500,000 RMB. We ended in a place that we thought was pretty good. But I think, you know, it goes back to the focus on products that are, you know, bring a lot of differentiation with them into a, you know, an unmet need, you know, a class that's providing an unmet need. You know, ZEJULA, I think is probably a pretty good example. You know, our net price now after a few rounds of negotiation, you know, a few cycles, you know, is somewhere in, you know, around two... You know, it's got individualized dosing, so it's not an exact thing, but it's around $2,000 a month on a net basis. I think when we look at those kind of prices, you know, plus or minus that, you know, on an NRDL basis, that's very... It's very good relative to trying to pursue just a supplemental insurance type of approach, which, you know, could yield prices that are, you know, maybe more like, you know, two-thirds or something of the U.S. price, but again, for only 10% or 15% of the population. The dynamics for us still feel very good. Makes sense. Specifically on the ZEJULA trajectory. I mean, is it fair to say that you're sort of out of the Covid headwind now with China reopening? Is there some expectation that the 4Q 2022 and the 1Q 2023 is still gonna reflect some of the pressures from Covid, or is that over now? Well, I think as at first, I think when we look for 2023, our view, even as people are coming back from LUNAR New Year and otherwise, we're starting to see, I think the light at the end of the tunnel as it relates to non-Covid utilization, you know, in hospitals and everything. We were, we're, you know, I think, quite optimistic about the remainder of the year in terms of patients able to get to the hospitals for their treatment. Our sales reps able to educate, you know, physicians on the benefits of Zejula and otherwise. I think we'll see a little bit of an impact in Q4. The impact was the, you know, the lockdowns that, you know, were being experienced across China. Again, the impact that means is patients weren't able to get diagnosed as early as they should have because they couldn't get to the hospital or something like that. I mean, Yigal, we haven't re-released our, you know, our Q4 results yet, but, you know, we've been pretty consistent in saying that impact in terms of, you know, sales of ZEJULA is gonna be more. It is real, and we'll see a little bit of that in January and the beginning of February. You know, we expect, you know, continued good growth, like whether you're looking at, you know, certainly year-over-year, but even quarter-over-quarter. The depression, you know, that we see from COVID impacts is not enough to, you know, prevent, you know, sort of quarter-over-quarter growth. Again, I think we're quite optimistic about the growth prospects for ZEJULA and for the business overall for 2023. Yeah, there's no doubt. I think if you look at the PARP market overall, you know, in the, you know, toward the end of 2022, you'll see, you know, it didn't grow as fast as it, as it could have or should have. Again, that's gonna be because patients just weren't getting diagnosed or treated as early as they could have. Of course, that's, you know, terribly unfortunate. I think going forward, we'd expect to see really good, you know, really good growth. I think we're positioned really well from the ZEJULA perspective. You know, first line, you know, sort of, all comers, opportunity is big. About 60% of our sales are in first line today. That's where we'd expect the growth to continue to happen in 2023. You are now, as I understand, have dominant share or highest share. I don't know if it's majority share, but highest share in the PARP class in China, you've taken over from LYNPARZA. You're also saying that in addition to share capture from LYNPARZA, you are growing the market as well with the growth in the first line. Both are working in your favor, yeah? Yeah. Yeah, for sure. I, you know, I'd say as you know, the data, you know, sort of the market share data in China is not as crisp, I guess, as it is in the U.S. We look at two different share things. I think if you look at just overall value share across the PARP category, we're I think we're gonna close the year at about 39% share. I think that's gonna be a little bit below LYNPARZA, but LYNPARZA's got reimbursement in prostate, for example. When we tease it down to ovarian cancer patient shares, I think we're pretty confident that we're in the lead and that'll continue to grow. It's mostly gonna grow this year from, as you mentioned, growth in first line, all comers. It's gonna be new patients who, you know, otherwise, you know, historically wouldn't have gotten a PARP are gonna get Zejula in first line. Again, we'd expect that, you know, we'd expect the overall value share actually that in 2023 for us to be the number 1. We've got to be number 1 by a considerable amount in ovarian cancer to cover, you know, the fact that LYNPARZA's got prostate cancer as well. Okay. Yeah, no, that's a good, a good detail, which I don't think most people don't realize. Okay, just moving on to some of the other products. efgartigimod, just remind everybody that that product should be approved by the middle of the year. Is that, is that right? I think you mentioned you're building out a 100-person sales force. Just talk a little bit about more the commercial plan there. Yeah. We submitted the BLA last summer, so, you know, there's not a PDUFA date in China. You talked about our historical success in terms of regulatory, you know, timelines. I think historically, in general, somewhere between 12 and 18 months is what's fair to assume from submission to approval. We're focused on trying to get that to happen within 12 months, so that would be by this summer. Of course, patients, you know, are waiting for this drug. The other benefit of being approved, you know, earlier rather than later in 2023 is it gives us the chance to negotiate for, you know, for an NRDL listing in early, you know, 2024. So, you know, we don't have a definitive date, but so far the regulatory interactions are going well and as expected. Some as early as this summer to the second half of this year is probably the right expectation. We're planning for this summer. We are hiring. We're, you know, completing the hiring plans for a 100-person sales force to launch GMG. I think when we look at myasthenia gravis in China, it's about 200,000 patients. They're in registries. They tend to be even more concentrated in terms of where they seek care, more concentrated than Zejula. We think with a 100-person sales force, we can get the vast majority of the physicians and patients who are seeking treatment. I think if you look at that 200,000 number and start to, you know, factor down for patients who aren't responding well today to current therapies, you know, there's a clear 50,000 plus, you know, patient opportunity, you know, sort of day one. We want to I think with a 100-person sales force, we should be able to get to that pretty quickly. We'll submit for. This is for the IV administration. We'll submit for subcu later this year. We also are in, you know, in all of the other phase three trials that Argenx is running on a global basis. We're running the China portion of those, you know, those trials. We're, you know, anxious for, you know, the readout in CIDP, you know, coming up here soon on a global basis. We're part of that trial. ITP and PV are, you know, coming, you know, soon thereafter. I think from an efgartigimod perspective overall, going back to some of our earlier comments, I mean, there's a, you know, really significant opportunity here. Myasthenia gravis alone, I think, you know, is a really compelling opportunity. You start to stack in some of the other indications and, we're, you know, really excited about this opportunity. Okay. The other big one or one of the other big ones in the neuroscience vertical is KarXT. Help us clarify a little bit the timelines there, ’cause, you know, obviously we already have the phase 3 data from the U.S. study. The way you characterize it in the slides, I think, is sort of a medium to longer term approval. I’m just wondering why that isn’t more proximal, a sooner approval. I know you have to do some bridging work, but just help us understand the timelines for getting that one on the market in China. I think first we are, you know, we've announced that we're starting a bridging program in China. We have approval on that program itself, and it'll start enrolling patients in the second quarter of this year. I think the reason that we have it a little bit, you know, out a little bit longer, I think everything else that we're, you know, saying is in the next two to three years, you know, even under the most conservative cases, you know, in terms of the regulatory path, they fit in that window. Our goal, of course, with KarXT will be once we start the bridging program, you know, to be able to leverage the FDA submission and approval in conjunction with the bridging program and try to get that to happen. Like, goal is to have a launch in the next, you know, few years. You know, we need to get going on the program and continue the regulatory, you know, interactions and otherwise. I think, you know, I think it's fair to assume, you know, that in the U.S., you know, provided everything goes well for Karuna, you know, there's an approval sometime in 2024. You know, we'd like to be, you know, as close to that as possible, given the bridging program and other things we're working on. We'll give more details as we, you know, as we get into it. There's, you know, there will have to be, you know, negotiations and otherwise along the way to try to speed that up as much as we can. You know, I think the, you know, the more conservative date probably pushed into that, you know, that, you know, 2025+ timeframe. Certainly we've never, you know, I think historically we've always done better than the conservative timeframes there. Now, the opportunity is really significant here. You know, I think, there are 8 million patients with schizophrenia in China, at least half of whom are in a, you know, are in registries and actively seeking care in, you know, concentrated, you know, site wards or hospitals in China. I think this is one, you know, going back to my earlier comments, it was compelling enough and big enough on a standalone basis and such, you know, innovation that we thought it made sense to use this as a, you know, as a way to start in neuroscience. I think, you know, as we think about opportunities to invest behind the launch here, it's probably, you know, at launch somewhere, you know, in terms of overall people and targets, it's somewhere probably between what we're talking about for efgartigimod initially and you know, where we are for ZEJULA, which has about 450 sales reps right now supporting it. You know, we're still in a pretty concentrated launch, but for a, you know, very significant number of patients. Okay. Just remind us, everyone, what exactly has been asked for with regards to the bridging work, or is that still being discussed or is that already sorted out? I mean, is it... I'm assuming you're gonna need to show the obvious things like the PK comparability and safety, but how much actually on efficacy are you gonna have to demonstrate relative to the US claims? Of course, you know, you know this space, right? I think in neuroscience it's the, you know, there were no Chinese patients in EMERGENT-2. You know, the biomarker or even, you know, PK data is probably not exactly, you know, it's not enough here, right? You need to see some kind of efficacy because it's neuroscience and it's not as biomarker, like, driven. I think, you know, we certainly need to show some trends in efficacy. We don't need to, you know, we're not running a full phase 3 program or anything there. As you know, these are short-term studies to begin with, right? You know, we'll be able to leverage the safety data and otherwise from a global perspective. Our bridging program and we haven't given, you know, sort of full details on it, does, you know, look at efficacy in schizophrenic patients in China. It doesn't need to be a fully powered, you know, phase three program. I think that's where I'd say I put all those things together, Yigal. Our goal will be to get all of that done and be in a position that, you know, soon thereafter the U.S., you know, approval as it comes, you know, we've got enough data to be able to, you know, significantly, you know, to being able to significantly discuss the, you know, the regulatory path possible. I guess I'd put that back to, you know, well, at adagrasib we're in a similar position. You know, we're now more confident on the end date there because there's been a U.S. approval and otherwise. I think that's, you know, I wouldn't read too much into where we put on the chart. It's just we're, you know, we're already a step behind there in that there hasn't been a U.S. approval yet for us to leverage in regulatory discussions. We do, we are starting the bridging program. That's, you know, for us, the best case is, you know, I mean, when we haven't participated in a phase 3 is you have a U.S. approval based on phase 3. We've started a bridging program, and we're part of broader next generation phase 3 programs. We're gonna have all of that on KarXT, and we'll be waiting for the U.S. approval that, you know, really, try to, you know, make sure that we're speeding up the regulatory path as much as possible. Okay. Okay, maybe if we could just kind of run through kind of lightning round, I guess. Yeah. You have so many assets, we can't get to everything. Right. Right. Right. Right. Just I think to help people understand what's likely this year versus say, 2024 in terms of some of the near term approvals. I mean, my list I have TIVDAK is one, MARGENZA, the MacroGenics, Odronextamab, Repotrectinib, Mirati one we talked about, the FGFR2b, and then the antibiotic, the SUL-DUR. Yeah. Can we just kind of run through super fast, just rough, roughly where those, where those might fall out in the, in the next, say, 18- 24 months? Yeah, sure. Well, I think, you know, I mean, maybe the most broad, relatively, you know, soon approval is, you know, we're working through the final aspects of submission there. I think, you know, for us, that's probably a relatively, you know, in terms of the products we really care about in terms of commercial opportunity. That's probably one of the smaller ones, but that's close. Sorry, Josh. You cut out for a sec. I didn't hear which drug you were referencing. Oh, MARGENZA. the MacroGenics. Okay. Okay. Yes, yes. I think that's. We're in the final process of submission there, so that should be a relatively, you know, sort of near-term. Similarly for XACDURO, we've already submitted, you know, it's got breakthrough, you know, priority review process. You know, it's an antibiotic complex, so we'll see how. You know, there's probably a lot of review stuff that goes into that just because it's, you know, it's sort of a combo product and otherwise. That's one that we should expect regulatory action on, you know, sometime in the next 12- 18 months for sure. Those are probably the two closest other than efgartigimod, which we've already talked about. I think then, you know, we said, Repotrectinib, we are having a pre-NDA meeting with NMPA later, you know, in this quarter, and we'd expect to submit, you know, sometime by the end of the year. You know, again, that's also in conjunction with personal hires on a global basis. So that's a, you know, a more near-term one and of course then, you know, as I mentioned, the review process on these can be anywhere from, you know, 12- 18 months. Of course, with efgartigimod, we're, you know, subcu's the next piece we'd submit this year and expect regulatory action in 2024. Adagrasib, we're in the midst of, you know, of regulatory discussions. you know, as I alluded to in our KarXT discussion, you know, we leverage the US accelerated approval. We've already started our own bridging program, and we're part of the confirmatory, you know, phase 3 KRYSTAL-12 trial. Those things together, you know, are, the package now that we have, regulatory discussion because that's not a date, it's a negotiated discussion. We'll, you know, we'd expect to, hopefully have that, you know, have that on the market sometime in the next, you know, in the nearer term, in the, in the 2-year period, as well. I think on bemarituzumab, our big, this is gastric cancer, in conjunction with Amgen, we'll join their FORTITUDE-101 study this year. You know, as soon as that's complete, we would look to leverage that submission. Of course, that's, you know, that's gonna be sometime more in the 2025 timeframe. We talked about KarXT. Let's see. I think those are probably the most proximate. I'm trying to think. Well, okay, of course, LUNAR, which is probably want to spend a few minutes on that. You know, our expectation is as Novocure has said, you know, there'll be a full data reveal and readout at a major medical meeting sometime in the middle of this year. You know, I think the speculation is ask so, but that's, you know, that's. I don't think they've said anything, you know, hasn't been accepted or anything yet as far as I know. But that, they are preparing to submit the second half of this year for approval, and we participated in LUNAR, and we have enough Chinese patients and sites and data to trigger a submission. We don't need bridging work or anything in China. We would trigger our submission off of the U.S. submission and, you know, try to do that as soon thereafter as possible. The process is, you know, a little different because it's medical device, but for the most part, it's pretty comparable. We would look to be able to submit LUNAR for Chinese approval as early as the second half of this year. Again, that's gonna be triggered off of what Novocure does in the U.S. I think those are probably. I'm trying to think if I missed anything there. I think those are the big hits so far. TIVDAK. Oh, yeah. TIVDAK we're. We've joined the confirmatory phase 3 trial. Again, we'll be in regulatory discussions to try to leverage the accelerated approval and the fact that we are now in the confirmatory trial to try to speed up that approval in China. I think those probably cover the, you know, 7 or 8. Odronextamab. You know, the pivotal, what could be a pivotal phase 2 study should complete this year. You know, I think particularly if you look in, you know, follicular lymphoma, I think the data there is pretty exciting. We'd look to, as quickly as we can, you know, begin, you know, regulatory discussions and submissions for approval there. I think. That's the CD20/CD3? Yes. Yeah. Yes. That's right. With Regeneron. Regeneron. Yes, with Regeneron. Yeah. Yeah. I think the data in, you know, in DLBCL looks pretty good too. You know, we'd have to look and see what works there. Again, I think that data will be, I think, relatively complete by the second half of this year, and we'll see what position that puts us in for a potential, you know, submission in China. Okay. Well, let's talk about LUNAR because. Okay. Presuming that is gonna be the. It is kind of a big data readout. I mean, you had the top line, which gave us the headline, but we don't have a lot of the numbers. Obviously, the stock obviously benefited very nicely from that readout, that's great. I have been getting a lot of questions on it and, you know, I think people are trying to understand a little bit what the conclusions will be when we see the full data at ASCO. I mean, it was not a simple trial in the sense that it started. I believe if you look on clinical trials, it started December 2016. Yes. Yeah. Yeah. At that point it was kind of billed as a trial for platinum failures. As you know, the landscape shifted rapidly with KEYTRUDA approval in May of 2017. Then again there was a second one in squamous in October 2018. Yeah. You know, a lot of people are saying, well, okay, well, it was a platinum failure as a design, but from a sort of de facto basis, most of the patients did receive some form of IO in the front line. Therefore, you know, maybe more of them received the docetaxel plus the TTF in the second line, given that they probably wouldn't want to retreat them with the IO. You look at the data, and obviously you trended on the docetaxel plus TTF, but didn't hit stat sig and you did hit stat sig on the overall study, obviously, which the obvious inference is that the IO plus TTF made a very significant difference in pushing you over to statistically significant territory. You know, that's kind of the backdrop. All of this you obviously know. Right. That's been kind of the question as to how to think about this in terms of the applicability of TTF in this sort of situation. Anything you can say there would be very helpful. Yeah. Of course, you know, I can't say anything about the subsequent 'cause that'll be, you know, presented at a medical meeting. What I can say is, you know, we participated in the trial. We enrolled our patients at the end of the trial. You know, we have said that the patient set that we have, which is, you know, a subset of course of the overall LUNAR data, is representative of standard of care. The majority of patients, you know, that we enrolled did have checkpoint in first line. You know, again, we'll have to see the data, but our plan, I can tell you what our plan is, you know, is to be ready to submit, you know, post Novocure submission. Our plan is for a broad label in second line so that, you know, it's gonna be Tumor Treating Fields, you know, in conjunction with whatever, you know, the physician choice for standard of care is in two second line there. Based on what we know of the trial design and data, we are expecting a broad, a broad label and a broad approval. I, I can't, you know, can't dispute any of the sort of, you know, speculative analyses you do based on, you know, what we've seen so far. I think we're, you know, we moved from, you know, I think we said we moved from cautiously optimistic about the opportunity with probably an emphasis on cautious, to, again, from everything we know and we don't know more than, you know, the top line data and but we know, you know, when we enroll patients and otherwise. I think it's, you know, I think I would say at this point we're all gonna see and learn more about the data, you know, in the coming months. Our, our view is the trial was powered for overall survival. It hit, I think the, you know, the, the sub-analysis and what Novocure said in the press release was that, you know, both, you know, while one was statistically significant, the other trended toward, you know, toward benefit. Again, I think a lot to learn from the data itself. Our, our view is it's, you know, our base case is we're gonna be submitting for a, for a broad second line label and that our data in China will be, you know, supportive of that submission. If that's the case, right? Again, there's a lot of ifs there, right? If that's the case, we see a really compelling opportunity here. I think the biggest positive development beyond the trial itself is the move in China toward making innovative medical devices eligible for reimbursement, as early as 2024, but I think certainly by 2025, when that probably is the window that we'd be looking at, a potential, maybe, we could maybe have a potential approval in 2024, but for 2025, if we could have this be available for broad reimbursement, I think that's a that could be a huge commercial opportunity, right? You know the numbers, 700 or 780,000 new patients a year diagnosed with first-line lung cancer. Of course, they're gonna progress, you know, so you start to do the factors on the numbers, you don't need to have much to get to a pretty compelling, you know, sort of patient number. Our experience with Optune has been, you know, it all kinds of other considerations where we think this is gonna be a meaningful technology in China. I mean, if you can comment when, you know, when we see the data at the medical meeting later this year, will we be able to see some of the subgroup work? For instance, looking specifically at the China patients and basically checking the box that obviously it wasn't powered just for the China patients, nonetheless that the conclusions there in that subgroup were consistent with the overall study or if you can say that now, that would also be great, I don't know. I can't say it now, I can't comment. I mean, Novo owns the data disclosure here. Of course, we will you know, as a partner, we're gonna be, you know, closely aligned and all those kind of things. I think that I certainly know that part of the reason to have a, you know, a, you know, relatively brief description of results in the press release was to preserve the opportunity to go into, you know, into good depth at a major medical meeting. I can't give you all the details on which subgroup analyses will be shown and otherwise, but, I mean, I certainly know the plan is to, is to, you know, to use the medical meeting to fully, you know, elucidate the data in the trial. You know, you certainly will have from us post-meeting, you know, you'll get the view from us on what we're gonna do with the data. Again, unless or until you hear otherwise, you should assume that our view is this is gonna be, you know, moving full speed ahead on, you know, preparing our submission and preparing for a broad, you know, second line label. Okay. Let's just switch over to your internal pipeline. You mentioned. Yep. The IL-17 human antibody earlier. I mean, according to what you've stated, I believe you said it's gonna be in a global phase 2, either end of 2022 or basically any day now, early 2023. Can you comment on where that one stands as you kicked off the global phase 2? I think you've also commented around potentially partnering that in the other direction, meaning to people outside of China, that maybe United States or Europe. What is that still the game- Yeah. Can you hear me? Oh, hi. Yeah. Can you hear me? Yeah. Yeah. Okay. Is that still the game plan in terms of the partnering, you know, essentially like the? Yeah. Licensing strategy? I think so. First, we will start a phase 2 program this year. Our challenge over the last number of months has been CMC, ensuring we have enough product to begin and complete the phase 2 program. We're working through those pieces now. I think, you know, if everything had worked perfectly, we'd have started the global phase 2, you know, in the fourth quarter last year. It didn't work perfectly. These are all solvable issues. You know, we're getting to the point now where we're building enough supply that we can start and finish the trials. I think, yes. I mean, I think we're quite excited about. You know, there's really a novel, you know, opportunity here. If we can, you know, in a broader setting, demonstrate IL-17 like efficacy with, you know, topical safety, which is the goal here, that opens up a very broad, you know, opportunity in psoriasis. We probably alone are not the best company to, you know, to fully leverage that opportunity because as you know, there are very big players here in, you know, around the world in psoriasis and in these markets. To, you know, to, I say, fully, you know, take advantage of this novel technology, a partner probably makes sense. If, you know, we need to get into phase 2 and, you know, I think that the right time to partner would be in the next, you know, year or 2 as we're beginning the study and otherwise. Again, I think our hope is that this is a very compelling technology and as such with some data, it'll attract interest from others, and we're gonna continue to invest in this and push it forward. You know, I think if we get to the, you know, to the point of beginning to plan for commercialization, so while we're still in, you know, phase 3, I will be reluctant to want to do this one on our own. There are gonna be other things in our pipeline, but, you know, if it's a gastric cancer opportunity in the U.S., we've got really good expertise there. I think those are things that we could, you know, choose to do ourselves. I think, you know, broad immunology in the US is for sure, I think, companies who are better positioned than us to do that. It doesn't mean we may not be part of that, but, I think we would look for a partner here. Okay. That makes sense. I know we're just kind of at the top of the hour, but maybe just last question. I think you talked a lot about at the beginning about the innovation aspect and how you're differentiated there. What's next? What's the next asset after the IL-17 that's getting close to a clinical study which is being derived from your internal R&D engine? Yeah. You know, we have a claudin antibody in Phase 1 that I think you know, we think it's got an opportunity to be differentiated. I mean, that's, you know, that's a growing interest class and competitive, but I think that's one that, you know, we're hopeful that there's differentiation. I think the next is our CCR8. You know, on the immunology, you know, sort of I mean, oncology, but in the oncology side, that's one that we'd expect to, you know, to start and begin to generate clinical data in this year. I think that's a space that, you know, is interesting, but I think still pretty open. Those are the two for this year, I think I, you know, I'd look at in terms of actually, you know, generating some, you know, some clinical interest and validation. Okay. Thank you. This is great. I know we could probably keep going for another hour or two, but we have limited time. Thanks, Josh. Appreciate the time. Okay. Very interesting, and, I'm sure we'll be chatting very soon. Yes. No, thank you. Sorry about the technical issues on my side. Thanks for being patient. No worries. No, it's- Listening. Okay. All right. Okay. Thanks. Thanks, Yigal. Okay, bye.