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Citi's 2024 Global Healthcare Conference

Dec 4, 2024

Yigal Nochomovitz
Analyst, Citi

Welcome back, everyone in the room and listening on the webcast. I'm Yigal Nachamovitz, one of the biotech analysts here at Citi. I've been covering Zai Lab since the beginning, since the IPO back in, I think, 2017, and so it's my great privilege to have with me the President and Chief Operating Officer, Josh Smiley, who's been at Zai Lab now for a number of years from joining from Lilly. So welcome. Thank you so much.

Josh Smiley
COO, Zai Lab

Thank you. Thanks, Yigal.

Yigal Nochomovitz
Analyst, Citi

Reminder that if you have questions, you can type them into the website, and I'll see them on the iPad, and I can ask the questions, whether you're in the room or online. So maybe you want to just start with the big picture, the Zai Lab mission, where you are, the scale of your commercial operations. We're going to get into the pipeline.

Josh Smiley
COO, Zai Lab

Sure.

Yigal Nochomovitz
Analyst, Citi

Just to set the stage.

Josh Smiley
COO, Zai Lab

Yeah. Well, thanks, Yigal. Thanks for having us. And thanks for your support for many years. Yeah, Zai Lab's 10 years old, actually, this year. We have two, really two parts of our business. We do commercial business in China, partner with some of the best biotechs in the world who otherwise don't have good development or commercial capabilities in China, and have a portfolio now of eight approved products or indications in China. Biggest product is, from a sales perspective, is in ovarian cancer, Zejula. It's a market leader in the PARPs, which I think is probably the only place in the world where Zejula is a market share leader over Lynparza. So we're quite proud of that. Our fastest growing product is Vyvgart for gMG. That's in partnership with Argenx.

We've said that this year, which is the first full year of launch, will sell over $80 million in China. That would be, by all accounts, a blockbuster launch and probably the best immunology launch in China history. We have an emerging global portfolio of products that we have rights to, not just in China, but outside of China. Most recently, we released data on a DLL3 antibody in small cell lung cancer. That's a product that's in a phase one setting now. As we look at where we are, when we look at the commercial business in China, consensus is for this year somewhere in the $380 million-$390 million range in terms of sales. We see that number in China going to $2 billion by 2028.

We've given that kind of directional guidance, and probably $3 billion or so by the end of the decade. That's based on the products that we have partnerships with today. We said we'll be profitable on a cash basis by Q4 of 2025, and of course, growing profitability over time. I think with the DLL3 antibody as probably the clearest and fastest path to regulatory approval outside of China, we expect to have products on the market in the second half of this decade in markets outside of China. So that's who Zai is.

Yigal Nochomovitz
Analyst, Citi

All right. So a lot to dig into there. So let's start with Vyvgart, which is obviously top of mind given the launch. So give us a little flavor for how it's going, what's driving the launch. You have, obviously, the MG, but you also have the CIDP indication. How does that drive sales? And then there are other indications beyond that. There's a long list, actually, that could potentially come through over time. So just give us a sense there for, and how's the adoption amongst the Chinese hospitals?

Josh Smiley
COO, Zai Lab

Sure. Yeah, we're partnered with Argenx, of course, on a global basis here. We have the rights to all the opportunities in China that we opt into, and then we participate with Argenx in the global development. We provide the Chinese patients and sites. And as you mentioned, we were already approved in gMG, both in the IV form as well as in Hytrulo or the subQ form. And we recently were approved for CIDP. But we were approved in gMG June of last year, 2023. We import the product into China. So we had a commercial launch in September of last year. So we're just a little bit more than a year into the launch.

But in China, the real way to drive volume and uptake is through the National Reimbursement Drug List, which is a national formulary that covers somewhere in the range of about 95% of the population. We did achieve listing for the IV form for gMG in January of this year. So really, we're like one year into the launch for gMG. There are about 170,000 patients with gMG in China, so a little more than three times what you see here in the U.S. And the treatment paradigm is pretty concentrated. We're focused on about 1,000 institutions and about 2,000 physicians that cover the vast majority of those 170,000 patients. So far, what we're seeing is about 1,000 new patients a month are being initiated on Vyvgart. We've said that by the end of the year, we expect somewhere in the range of 12,000 or more patients who've initiated.

That's 12,000 against that 170,000 total base. When you look at the price that we have through NRDL, which is basically $800 per vial, but what's more meaningful is to think about this over the course of an annual course of treatment, which is about $32,000 in China. When you look at those number of patients and when they initiated and how frequently they're coming back for their cycles, we've said that in total, we'll sell over $80 million this year. What we've said is over time for gMG alone, you should expect an opportunity in the $500 million range. We were approved in CIDP as the next indication. CIDP, it's about 50,000 patients, so 50,000 versus the 170,000. There are no products approved today for CIDP on the NRDL list. This is a really significant improvement.

The data from the phase three trial that we participated in is quite compelling. As I mentioned, NRDL listing is important for affordability and access for patients in China. Given when the product was approved for CIDP, we won't be able to achieve listing in NRDL until 2026. Next year for CIDP, it will be selling into what's the cash pay or supplemental insurance market, which is a sliver, really, of the total opportunity. Somewhere in the range of probably 20% of patients have access to supplemental insurance or other things that can make the product available or accessible to them. As we think about 2025, Yigal, it's really around continuing to drive penetration in gMG.

So start to expand that 12,000 patients to something broader, ensure that they're coming back in for their cycles of treatment, getting the full benefit of the product, and beginning to launch CIDP with anticipation of a robust launch in 2026. As you mentioned, there are many other indications that we participate with Argenx on. I think the next big one that we've begun to join the phase three trial is in thyroid eye disease. And just to give a sense of scale, I mentioned 170,000 patients for GMG. It's in the range of 500,000 or more for thyroid eye disease. So a pretty big and significant opportunity there as well.

Yigal Nochomovitz
Analyst, Citi

And then you mentioned NRDL, which is obviously a feature of the China market, which we don't have over here. But how are you thinking about that aspect of the business case in terms of that comes up for renegotiation every so often? I don't remember the exact time frame, but you need to.

Josh Smiley
COO, Zai Lab

Yeah, so there's every two years.

Yigal Nochomovitz
Analyst, Citi

Every two years.

Josh Smiley
COO, Zai Lab

There's a mandatory renegotiation. Now, there have been the NRDL sort of process has only been around now for, I think, seven or eight years. And there have been some incremental changes over time. There's still a mandatory every two-year repricing. But one of the improvements that's been initiated or implemented over the last few years is what's called simplified renewal. So it used to be in the past that every two years you went through a full renegotiation of price. And in many cases, historically, that led to reductions of like 20% or more. The process that's in place now is there is an option to follow basically an algorithm that just it's a grid, and it says, how much have you sold over the last two years relative to your initial projections?

Based on that grid, you can opt for a mandatory price reduction of anywhere from 0-20%. That adds a lot of transparency to the process and predictability. It's not mandatory. So it basically acts as a floor. So you can look at that option, decide if you like it. And if you like it, you just opt in. If you don't like it, you go through the renegotiation process anyway. So I think as we think about that process, we think it's quite manageable for the IV form of gMG that'll be coming up for renegotiation in 2026, that we should be in the manageable price reduction sort of areas. And what we've said is probably somewhere in the single-digit types of declines on an every sort of two-year basis. Each indication, though, is also priced separately.

Yigal Nochomovitz
Analyst, Citi

That's a nice grid.

Josh Smiley
COO, Zai Lab

Yeah. So CIDP and the Hytrulo form of gMG, the Hytrulo basically is the form for both CIDP and the subQ version for gMG. That'll go through a separate process, and that'll be in 2026 as well. So again, I think our view is there are lots of reasons and lots of benefits that the subQ version brings to Chinese patients, including the opportunity for self-administration. So the label's a little bit different in China.

Yigal Nochomovitz
Analyst, Citi

Have you disclosed that?

Josh Smiley
COO, Zai Lab

Yes. Yeah.

Yigal Nochomovitz
Analyst, Citi

Okay, and how does that compare to what you just referenced?

Josh Smiley
COO, Zai Lab

So the IV form, of course, requires coming back to a hospital or an IV center. And that's an hour-long or so process, subQ's 60-90 seconds. In the US, though, that still requires, I think, a healthcare professional to administer it. In China, there's an opportunity for self-administration. So that's a big incremental benefit for patients and for the healthcare system. So we'll use all of that data to try to negotiate a good price for 2026 for the CIDP and subQ version for gMG. But for 2025, really, no price change from where we are today. So again, $800 a vial, $32,000 a year if you follow the prescribed treatment course. And really, the focus will be on continuing to drive gMG patients initiated and making sure that they stay on for multiple cycles.

Yigal Nochomovitz
Analyst, Citi

Okay. Very good. Let's see. Let's talk about DLL3 because that's an important one. I don't want to run out of time. So obviously, it's an interesting target. Pharma has done some notable acquisition activity in that space. Yours is ADC. Can you tell us a little bit more about the payload and the design of that molecule and what the plans are for globalization?

Josh Smiley
COO, Zai Lab

Yeah. Yeah. So this is an asset that we acquired from a company based in China, MediLink. And we like their ADC. They've got an ADC platform that we were attracted to, and we really like the DLL3 target. We did a deal with them last March or April when this asset was still in the preclinical phase. So very modest upfront, and we owe a single-digit royalty to MediLink over time as we commercialize the asset. We moved quickly from a preclinical asset into phase one study that began in January of this year. And we released data at the Triple Meeting in Barcelona at the end of October on patients with late-line small cell lung cancer, heavily pretreated, and showed an overall response rate in patients in about 24 patients, I think, overall response rate of about 74%.

So I think we were quite pleased with that data and a relatively straightforward safety and tox profile. So what do we see here? We see a couple of opportunities. The first is for late-line small cell lung cancer. We do see the opportunity for a potential path for an accelerated approval. As you mentioned, the DLL3 target is one that's, I think, well established and precedented. Tarlatamab is approved under a conditional approval in the U.S. It's a bispecific against this target. And I think it's got a lot of safety and toxicity liabilities associated with it. It requires hospitalization and monitoring. And otherwise, I think from what we see so far, we've got a cleaner approach here. So our intent is to expand the phase one study, pursue late-line small cell lung cancer in somewhere in the range probably of 100-200 patient study.

We're in the middle of the dose expansion phase of that approach. We've also said we're going to move into a first-line study in small cell lung cancer in combination with Atezo and chemo. We'll start that study in 2025. I think what we see with the ADC approach is an opportunity for this to get the kind of response rates and hopefully durability that you see with Tarlatamab, with less safety and toxicity liability, which then, again, makes it a more convenient product, certainly, for healthcare practitioners and patients to use in a late-line setting and an opportunity, I think, to do this in a first-line setting and potentially limit or reduce the tox burden or the burden associated with chemo in a first-line setting.

Yigal Nochomovitz
Analyst, Citi

And then as far as how you're going to develop it ex-China, as you're doing, are you going to go with a partner, or are you going to do this yourself? I mean, what's the plan? Because at this point, you've got all your commercialization in China, and so you need to build it.

Josh Smiley
COO, Zai Lab

Yeah. I think for small cell lung cancer in the U.S., we think we have the ability, capabilities, and otherwise to launch this ourselves. First, from a global development perspective, we've got a robust development team. As we talked about earlier, we participate in global trials with many well-established leading pharma and biotech companies. We've got a development organization that's in approaches about 800 people. So we do all of the work ourselves in China managing sites on a global basis. We have leaders for all of the functions that go into global development. So we'll lead development ourselves here. Even in the phase one study for DLL3, 60% of the sites were in the U.S. So we're marching along from a development perspective. We don't need capability enhancements or anything there.

I think as we think about commercialization in small cell lung cancer, given this data and this asset, what we expect is that we could commercialize ourselves, and that's our plan. Now, we're certainly open to partners or otherwise. But my experience has been if you can retain U.S. economic rights as long as possible and through commercialization, that's how you create the most value for shareholders. But we're going to be open to any approach. I think as you think about commercialization outside of the U.S. and China, we're certainly open to partnerships there. It wouldn't make sense for Zai to try to launch this product in Germany or France or something there. So I think if there are good partners who are willing to step up and participate and partner with us, we're going to be open to those discussions.

Yigal Nochomovitz
Analyst, Citi

By the way, when you introduced the guidance in the summer, it was June of 2023.

Josh Smiley
COO, Zai Lab

Three.

Yigal Nochomovitz
Analyst, Citi

Three.

Josh Smiley
COO, Zai Lab

Three.

Yigal Nochomovitz
Analyst, Citi

Yes. In New York at the R&D day. So you gave the sort of medium-term guidance of the end of 2025 breakeven. But there was some longer-term commentary. Back then, of course, you didn't know the DLL3 data. So I assume that that wasn't baked into those forecasts. Is that right?

Josh Smiley
COO, Zai Lab

That's right. I mean, we've certainly had global ambitions and aspirations. And we had a preclinical portfolio and a few assets in global clinical development. But we hadn't even, or we had just sort of completed the preclinical deal for DLL3. So I think as we think about our guidance, and just to reinforce the couple medium-term guidance points we've given, we've said we'll be cash flow positive or profitable on a company-wide basis in Q4 of 2025, full-year profitability in 2026, $2 billion in sale or 50% compound annual growth rate between 2023 and the end of 2028, which would get you about $2 billion of sales in 2028, and operating margins by the end of the decade somewhere in the range of 20%-30%.

I think DLL3, how does that change it now that we have an asset in front of us that we sort of know what we want to do with? I think it causes some pressure probably on the 2026 profitability, but I mean, not enough that we would in any way change how we think about the guidance or otherwise. The good thing I think we have, we have the capacity to invest broadly in DLL3 because you think about all the other products we just either referenced or we talked about like Vyvgart. Much of the investment that we've made into getting those products to launch or close to launch in China, there's a bolus of spend that's going away. We can redirect some of that spend to the phase three programs for DLL3.

I think for sales, again, I think we think there's an accelerated approval pathway here for DLL3 in the U.S., and that could certainly help the 2028 sales number. I think if that pathway is validated and we are able to execute against it, we should have sales in the U.S. by 2028 so that maybe make that number better. Certainly, by the latter part of the decade, we see this as certainly much more than a billion-dollar opportunity in itself in the U.S. when you look at the number of patients with small cell lung cancer and otherwise. So I think it should help. But we want to invest fully behind it, and we'll balance those things in the next few years.

Yigal Nochomovitz
Analyst, Citi

And let's just kind of, I know I've asked this in the past, but I think it's important just for people to understand the pieces of the puzzle that get you to that first goal of the breakeven by 2025. Obviously, Vyvgart is a significant piece of that, but that's not the only piece. So tell us what else needs to happen to get on that glide path. And as far as I understand, it's not about. It's not an expense game, right? It's a top-line game. So let's just go through all that.

Josh Smiley
COO, Zai Lab

Yeah. In fact, what drove the commitment around profitability was really what we saw on the top line, and what we have said consistently is from 2023 to 2028, we saw the opportunity to grow sales at a compound annual growth rate of 50% or higher, and that was based on the data that we have, the products that are already in development or launched in China, so I think if you follow a 50% number, and I think we're on a year-to-date basis, we've said, "Hey, that's over a five-year period. It doesn't mean you're going to grow over 50% every year, but we should be in that range," and we are. If you look at consensus this year, I think it would put us close to between 45% and 50% sales growth this year.

But so if you follow that out, you go for a few years into 2026, if you're growing at somewhere between 40%-50%, just using the math, and we certainly have the ability and capacity to do that. What it then requires is SG&A to grow significantly slower than that, but it doesn't require cuts or anything else, so it's a modest SG&A growth in the high single digits% to very low double digits% against, again, 45%-50% sales line, and R&D being relatively flat. By relatively flat, we've spent about $250 million a year in R&D over the last few years. As I mentioned, a lot of that went to late-phase China programs that are going to drive that sales growth. As those programs get to launch, we can take that capacity and put it against DLL3 and other things.

So, think about modest R&D growth, again, in sort of the single digits, maintain gross margin. Our gross margins today encompass both the cost of producing or acquiring the product that we sell in China and the royalties that we pay to pharma partners. But if we can keep that in the mid-60s to mid-60 range, the math then for 2026 is get you to profitability without having to assume anything unusual. I would say this year, we did take some now that we know what we have, we know what launches are ahead of us. And otherwise, we did take some actions this year to rationalize our expense base, get the resources in the right place. And I think you saw some of that show up in Q3, where SG&A was down on a year-over-year basis. We did all of those kind of things.

These were some headcount reductions, some changes in how we go to market for some of the smaller products that we have in China today. That was all done with the view of growing from here for the next few years, but growing in a pretty modest way. So that's how you get to profitability. Again, if we're not hitting the mark on Vyvgart, if we don't launch Bemirituzumab well, if we don't launch KarXT well, then I think profitability is a challenge. But what we see so far with Vyvgart, it's off to a great start. We're super excited about the next wave of products that are coming in China.

Yigal Nochomovitz
Analyst, Citi

Okay. Well, that's what I was kind of driving at for you to talk about KarXT and Bema. So what's the thinking as far as I mean, you did the bridging study.

Josh Smiley
COO, Zai Lab

Right.

Yigal Nochomovitz
Analyst, Citi

Check that box.

Josh Smiley
COO, Zai Lab

Yep.

Yigal Nochomovitz
Analyst, Citi

When could KarXT hit the shelves?

Josh Smiley
COO, Zai Lab

So we're in the middle of preparing the submission package now. So as you mentioned, we did hit the bridging study, hit both primary and secondary endpoints. So we're super excited about this opportunity for schizophrenia in China. We've said we will submit by early next year. We're working round the clock to get this submitted. And I'd love to see us get it done by the end of this year. But it's sometime in the next number of weeks, I would say. Then we have to go through the review process in China. There's not PDUFA dates in China. So if you look at historical averages, probably 12 months from submission to approval is a fair timeline to use. I think there are lots of reasons to believe that maybe this one can move a little bit faster.

I mean, there's a huge compelling need in China, lots of receptivity from the division in NMPA that looks at this, that this is a really important global technology and it'll make a big difference for Chinese patients. So I can tell you that we can't, because it's not all in our control, I think it's fair to assume an approval in early 2026, but we're going to be ready to launch in 2025. But I think that under a best-case scenario, I'd love for us to be able to introduce this product to physicians and patients in China by the end of 2025.

Yigal Nochomovitz
Analyst, Citi

Remind me, do you have rights to other neuropsychiatric conditions with this product?

Josh Smiley
COO, Zai Lab

Yes. Yeah. All of our deals would include the ability to opt into any other indications that the global partner, and in this case, now it's BMS, pursues. We already are participating in the global study psychosis associated with Alzheimer's disease. And of course, there'll be more patients with Alzheimer's disease in China than any other country in the world over time. It's an aging society and a big base of patients. So there's a really big opportunity here as well. And we're already participating in that trial. I think one of the things that was exciting to us about the BMS acquisition of Karuna, of course, we had great relationships with Karuna, was the capacity they have to invest in other indications as well. And we'll sit closely with them as they evaluate those.

I think certainly we'll want to lean in. I mean, given what we know of this asset and this mechanism, we'll lean into other indications as well as they sort of identify and decide to pursue them.

Yigal Nochomovitz
Analyst, Citi

Of course, this would go through NRDL too.

Josh Smiley
COO, Zai Lab

Yes. Yeah. This would go through.

Yigal Nochomovitz
Analyst, Citi

But it would be subject to steep discounting, or I mean, it's a much bigger market, 8 million schizophrenic patients.

Josh Smiley
COO, Zai Lab

Yeah. Yeah. Eight million patients with Schizophrenia.

Yigal Nochomovitz
Analyst, Citi

So you're not going to be subjected to some punitive discount, right? I mean, it's going to be what? Do we know yet what it's going to be?

Josh Smiley
COO, Zai Lab

We don't know what it's going to be, and of course, we own making that case and otherwise, but I think just a couple maybe sort of statistics. We have historically done really well in China negotiating a good NRDL price for China, not necessarily for the globe. But I think if you look at where we have achieved pricing, it's somewhere on a net basis for NRDL, somewhere between 10 and 20% of the US price. So I think the US price per day is in the $60 range, I think, for KarXT. So if you use somewhere between $6 and $10 a day, I think that's a reasonable starting place to think about pricing. I think if you put that number against penetration rates and otherwise, you can get pretty big numbers.

I think the other data point I would use is atypical antipsychotics are the standard of care in China. Of course, they're all now generic, but I think if you look at some of the branded post-NRDL pricing, they're in the $5 a day or so, so I think that somewhere in the range of $5-$10 a day is a reasonable place to start to think about where you could end up, and again, that's not a guidance or anything, but I think that's just based on historical precedence. That's probably a reasonable place to think about pricing.

Yigal Nochomovitz
Analyst, Citi

By the way, it just occurred to me a question I never asked because obviously it's China, so it's not an English-speaking country. When you do the branding in China, does the brand name sound like Vyvgart? Does it sound like KarXT in China?

Josh Smiley
COO, Zai Lab

It does. Yeah. Yeah.

Yigal Nochomovitz
Analyst, Citi

You sort of transliterate it?

Josh Smiley
COO, Zai Lab

Yeah. We use the US brand name as the brand name in China, and then, of course, we obviously use Chinese characters.

Yigal Nochomovitz
Analyst, Citi

Right. Okay. Got it. Just a bit of a detour there.

Josh Smiley
COO, Zai Lab

Yeah.

Yigal Nochomovitz
Analyst, Citi

Okay, and then Bema.

Josh Smiley
COO, Zai Lab

Yes.

Yigal Nochomovitz
Analyst, Citi

Bemirituzumab is important. Gastric cancer. This was the one that was, I think, discovered in Rusty Williams' lab, if I'm not mistaken.

Josh Smiley
COO, Zai Lab

Yes. Five Prime was the company, yes. And we partnered with Five Prime years ago when it was still based on limited patient data in phase two. Of course, Five Prime was subsequently acquired by Amgen, so they're our partner here. So we're studying Bemirituzumab in two global first-line phase three studies for gastric cancer. The first study, and we've said for both of these studies, the enrollment's complete. They're both overall survival studies, so we're just waiting for events. The first of the studies that we'll read out is Bemirituzumab in combination with chemo versus chemo, which is the standard of care today for first-line gastric cancer in China. That we've said should read out sometime early next year just based on the pace of events and otherwise. This study really replicates the phase two study, which showed, I think, pretty interesting and compelling results.

So we've got a lot of confidence that we're going to see a good result here. Of course, you don't know until you see the data. So what we're studying here is patients with first-line gastric cancer who overexpress FGFR2b. That's about a third of the patients in China. Now, just this one's probably a little under the radar screen for global investors because the rate of gastric cancer in the U.S. is not really high. In China, it is. There's 400,000 patients per year with gastric cancer. Because of the prevalence, it tends to be diagnosed early. So most of the patients are diagnosed in a first-line setting. That's where this product would play. The second study is Bemirituzumab and chemo in combination with a PD-1 versus PD-1 and chemo. That's the emerging standard of care, and that's a standard of care like here in the U.S.

That study, we've said, is about six months behind. It's also fully enrolled, so we're just waiting for events to accrue. I guess just in general, we have a little less confidence in that study. Not that we don't have high confidence in it. We just don't have a phase two to reference.

Yigal Nochomovitz
Analyst, Citi

That's in which line is it?

Josh Smiley
COO, Zai Lab

It's also in first line.

Yigal Nochomovitz
Analyst, Citi

Okay. And which PD-1 are you?

Josh Smiley
COO, Zai Lab

Opdivo, I think, is.

Yigal Nochomovitz
Analyst, Citi

Opdivo.

Josh Smiley
COO, Zai Lab

Yeah, and that's the only other drug that's been approved for gastric cancer in China for many years.

Yigal Nochomovitz
Analyst, Citi

Okay. So with those two data points, you could set up a filing.

Josh Smiley
COO, Zai Lab

Yes.

Yigal Nochomovitz
Analyst, Citi

I mean, just doing the rough math, I guess, end of.

Josh Smiley
COO, Zai Lab

Yeah. I would say best-case scenario is we've filed both of these studies in 2025.

Yigal Nochomovitz
Analyst, Citi

Okay.

Josh Smiley
COO, Zai Lab

By the end of the year and be ready to launch in 2026 with certainly NRDL listing by 2027. And again, you get into all the calendaring issues. But I think for sure this is a big contributor to the second half of our five-year growth rate commitment.

Yigal Nochomovitz
Analyst, Citi

But what's going to get you to that first goal of the break-even is the growth of Vyvgart.

Josh Smiley
COO, Zai Lab

Yeah.

Yigal Nochomovitz
Analyst, Citi

Whatever incremental growth of the base business of the original four products, and then in 2026.

Josh Smiley
COO, Zai Lab

Out of the gate with KarXT.

Yigal Nochomovitz
Analyst, Citi

You'll have two new launches potentially.

Josh Smiley
COO, Zai Lab

That's right. Yes. Yeah. Yeah. And of course, there are a series of other things we've had approved that will incrementally add to the break-even analysis. I wouldn't have time to get into a lot of detail on that, but like Xacduro, Repotrectinib. So we're getting really good products approved on a pretty frequent basis. And then I guess the other one to think about for the later part of the decade is TTFields. We were positively surprised.

Yigal Nochomovitz
Analyst, Citi

Okay. Let's talk about that.

Josh Smiley
COO, Zai Lab

We and everybody else, right?

Yigal Nochomovitz
Analyst, Citi

Can we talk about that?

Josh Smiley
COO, Zai Lab

Yeah. Sure. So we have a partnership with Novocure on TTFields. It's approved that this is the technology, basically. It's a medical device that sends electromagnetic pulses to tumors and has shown across multiple tumor types an overall survival benefit. We sell the drug or the device today under the brand name Optune for glioblastoma, and we've had this on the market for a few years, and market opportunity in China is in the range of $40-$50 million per year. It is not reimbursed through NRDL. That's a policy decision. It's not specific to Optune. Medical devices currently aren't eligible for NRDL listing. So we're only able to tap into the self-pay market, and self-pay really means self-pay, commercial insurance, supplemental insurance.

That, by our estimates, is somewhere in the range of about 20% of the population in China has the ability to afford or to access drugs like TTFields. We participated in the LUNAR study, which was in second-line lung cancer, saw a positive result there. We had Chinese patients participate in that trial and are preparing the submission package in China. It was just recently approved in the U.S. There have been, as you know, lots of controversy around how meaningful that data is in a very crowded, competitive, and evolving space in lung cancer. We participated in the pancreatic study. This is in first-line, unresectable pancreatic cancer. And of course, nothing has worked here. So I said we were surprised. We weren't surprised. We very much value the technology and had a lot of hopes for this.

But I think anybody who's doing a first-line pancreatic cancer trial should have a lot of.

Yigal Nochomovitz
Analyst, Citi

A little hubris.

Josh Smiley
COO, Zai Lab

Yes. Exactly, so I think what we saw in the data that was released on Monday is a little bit greater than two months survival benefit in first-line pancreatic setting. First trial that has shown an overall survival benefit in this setting. Novocure, and we did a press release very high-level just to mention a couple of data points, but there will be a more robust presentation at a medical meeting in 2025, and we're quite excited by this. It's a game changer, I think, in terms of how we think about this asset.

Yigal Nochomovitz
Analyst, Citi

What do you think the market is missing here? Because, I mean, obviously, Novocure reacted quite well and you didn't get the same response in the markets.

Josh Smiley
COO, Zai Lab

Yeah. And I think that's, I mean, as you can tell, we're quite excited by this opportunity. But I think to be fair, we have been cautious on how big of a contribution TTFields will be to our near-term results. It isn't reimbursed through NRDL today, so we're in a more restricted setting. That being said, I think there are lots of opportunities when you sort of now look at across multiple tumor types. We're seeing survival advantages. Pancreatic, of course, there's nothing otherwise other than chemo that is beneficial here. So I think there are lots of reasons that investors over time should start to get more interested and excited about the overall opportunity in China. And I think we haven't talked that up a lot, frankly.

Yigal Nochomovitz
Analyst, Citi

What's the logic around NRDL carving out the med device? Is that just a?

Josh Smiley
COO, Zai Lab

That's been a national policy decision.

Yigal Nochomovitz
Analyst, Citi

Is that something that's going to evolve or we don't know?

Josh Smiley
COO, Zai Lab

It's been evolving, and there have been movements and pilots in place to make medical devices eligible for NRDL listing, so again, this isn't an Optune or TT Fields. This is all devices. I think there's lots of reasons to believe that over time, maybe by 2027, there's an opportunity for a technology like TT Fields to be listed on NRDL, and of course, that would open up a much, much, much bigger opportunity than what we see today, but even at the supplemental insurance cash-paying market, again, just to reference, if there's a $50 million type opportunity in glioblastoma, the pancreatic just size of the market is at least three or four times that. So I mean, even if you're restricted to a smaller patient population that has access to insurance, we know this is also a much longer duration of therapy than you would see in glioblastoma.

So even without changes, we see this as multiple hundreds of millions of dollars of sales opportunity in China.

Yigal Nochomovitz
Analyst, Citi

Okay. Two more things before we wrap up. BD plans. I mean, that was obviously the genesis. That was Samantha Du's sort of vision to bring assets in from the United States or Europe. You've got a lot, obviously.

Josh Smiley
COO, Zai Lab

Yeah. Yeah.

Yigal Nochomovitz
Analyst, Citi

What's the pace of BD going to look like? I mean, obviously, you did raise a little more capital recently. So can you help understand? Was that to fuel more BD, or was it just to give you a little more cushion? Or what was the thinking there?

Josh Smiley
COO, Zai Lab

Yeah, so I'll start with BD. Of course, the company built the portfolio that we have today around business development and acting as a partner for Western Biotech, basically, and over the last few years, given all the things we had to work on, plus just the universe of opportunities, we haven't done a new big interesting deal in China. The last thing we did was Tivdak, which is going to be a really important product in China. But we do see a couple of good ones on the horizon, so you should expect us on an annual basis to do one or two late-phase opportunities to bring into China that sort of mostly fit into the therapeutic areas we're in today. Those aren't super capital-intensive.

As you know, Yigal, we tend to spend in the tens of millions of dollars upfront, and then we step into the investment by participating in the global development plans. But we do expect to further build the portfolio in China. Where we do see the more exciting, I guess, or robust opportunities are in the late preclinical, early clinical global phase. And we did a deal last quarter around an ROR1 antibody again from a Chinese company. Preclinical, we'll move it into the clinic next year. We'd expect to do a couple of deals like that per year. And the raise that we did gives us a little bit more capacity to do those deals and gives us a little more cushion. We ended Q3 with a little more than $700 million in cash, and we're headed to profitability.

The raise, which was only $200 million, wasn't necessary to do the next deal. It does give us the firepower and capacity to continue to move at, I think, a robust pace from a business development perspective going forward.

Yigal Nochomovitz
Analyst, Citi

There's a lot we didn't get to. I just realized we didn't talk about the topical IL-17, but we'll have to save that for the.

Josh Smiley
COO, Zai Lab

We'll do that in the next one.

Yigal Nochomovitz
Analyst, Citi

Next one.

Josh Smiley
COO, Zai Lab

Okay.

Yigal Nochomovitz
Analyst, Citi

So thank you so much for the time. Great to see you.

Josh Smiley
COO, Zai Lab

Thank you. Thanks, Yigal. Thanks, everybody. Okay.

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