All right, good afternoon, everyone. Thanks for joining us here for Jefferies Global Healthcare Conference in London. Sitting next to me is David Ng, Head of IR of HUTCHMED, and my name is Clara Dong, one of the biotech analysts here at Jefferies. David, before we go into specifics, I will hand it over to you to maybe set the stage by giving the audience an overview of HUTCHMED's pipeline and your commercial products, and what's your current focus?
Sure. Thank you, Clara. Thank you for having me again to this very wonderful conference, which is getting bigger and bigger every year, I notice. Let me start off very quickly with this slide here, which I think is a very good, you know, one-minute overview of where we are and where we're heading. I think on this side, on your left-hand side, you know, we are definitely a globally commercialized company. As Clara mentioned, we have a product already globally selling by Takeda. This is called FRUZAQLA. It's a colorectal cancer drug. Half-year sales, about $160 million. This is an in-house developed product through, you know, our scientists in HUTCHMED. And then, you know, we have commercialized in China already and is selling all around the world. We're looking forward to a second one. The second innovative drug is called ORPATHYS.
It's a c-Met inhibitor for lung cancer. Again, we have already commercialized in China. Our overseas marketing partner, as well as our China marketing partner, is AstraZeneca. AstraZeneca is working in a phase three trial for lung cancer, already completed recruitment and data readout is first half next year. We look forward to hopefully getting it approved in the U.S. and around the world in 2027. These two, I think, will be the most important late-stage product. The important thing, of course, is not just validate our science and the good work by our scientists, but it also makes us profitable. Either through the sales, the operating profit, as well as the upfront payment and milestone payment associated with these products, this has made HUTCHMED profitable since 2023.
That's kind of where the snapshot of where we are and also where we were in the past. The big thing that we will elaborate definitely more is our next-generation platform on your right-hand side, this ATTC next-generation platform. We call it an even better version than ADC because it's chemo-free. We still have a large molecule antibody, a linker, but then we tack it onto a small molecule targeted drug on one end. Maybe we'll elaborate a little bit more later on.
Great. We'll definitely touch on that a little bit later. Before we go into all those details, I mean, you're obviously one of the leaders in China biotech, and, you know, there is a rising interest in China biotech as well. You have this in-house R&D capability, and then you have global partnership and this extensive pipeline. Maybe talk to us about, you know, with this recent biotech environment, how are you prioritizing between growth in China versus global?
China definitely is still our base, a very important base, right? All our scientists, our manufacturing facilities, as well as our sales team are based in China. They provide a very good foundation on not just the discovery of new molecules, but it's also a very good foundation of our commercial success. I think it will remain so. I think we will definitely come up with even more exciting new molecules from our base in China. However, as you may all know, China is a very competitive space. Apart from a lower price and more competitive environment, it's also potentially less margin coming out from our China market, which makes also our overseas expansion very important.
You know, the fact that we have our FRUZAQLA selling in the US and Europe and Japan brings us a profit in several multiples than that we can obtain from China. I think we will continue to have a balance, right? I mean, on one hand, you know, the speed and the cost of production and discovery are much more efficient in China. At the same time, from the commercial angle, we will definitely continue to explore to bring our products to all around the world, but very likely to be through our partners. I think this is a decision we made three years ago. Instead of using our own sales team, we rely on established multinational pharma and a very efficient marketing engine to help to distribute our products to patients all across the world.
Maybe let's quickly touch on top line and bottom line as well. I mean, you guided 2025 oncology revenue to $270 million-$350 million. How should we think about the building blocks for that revenue guidance? Maybe in terms of profitability, how should we think about the financial sustainability moving forward as well?
Yeah, so we have recently revised down our full-year revenue guidance on the back of some of our products. Sales seems to be a little bit disappointing in the first half. That's due to, I guess, two reasons. Number one, again, the increasingly competitive landscape where some of our products start to see our competitors having generic. That's one reason. I think secondly, and I think this is even more importantly, is that we have decided to restructure our sales infrastructure to be even more compliant. We have reduced a certain type of sales activities in some kind of more remote hospital and kind of lower-tier cities. You know, the result of that is actually we have reduced the headcount of our sales staff and, as a result, lowering sales expenses. In the process, our sales was impacted negatively, but we think it's a temporary thing.
In the second half of this year, actually in the month of June, July, we start to see sequential improvement in our sales in China already. I think, you know, this exercise actually positions ourselves to have a much more sustainable sales infrastructure, not just for our current portfolio products, but also for our future products we're going to launch.
Great. Now let's talk about your ATTC platform, antibody targeted therapy conjugate. You recently hosted an investor event for this very exciting platform. Maybe just talk to us, maybe for those who are less familiar with this platform, what's really the difference between this modality versus traditional ADCs? What are the key differentiators there?
Sure. This is something we are very excited about. I think if this, I have to say, if this actually turns out to be successful, the value and the potential of this ATTC platform may be bigger than everything we have done in the past. I think one of the key factors is that if you look at the structure, we still have the antibody, that Y-shaped antibody, large molecule. We still have the linker. The payload is different from the traditional ADC in that it is going to be a small molecule targeted drug. Instead of the chemotoxin, which, you know, to a certain degree, they are kind of undifferentiated and can result in off-target toxicity, we have replaced that payload with a small molecule targeted drug. Our thought is that this will reduce the toxicity and improve the selectivity.
We have already got some very good data in the preclinical stage. We actually also presented some of this data in the recent ULTC, the triple conference, and also in our R&D day. Next month, actually two weeks away, or three weeks away, we're going to start human trial in phase one in both China and U.S. We will start to see the impact on human patients. It's still predominantly targeting oncology. One thing I would like to point out, again, if this works, I think this may also have the potential to be applied into frontline oncology indication. Remember, ADC still has the chemotoxin in it, but we call our platform to be chemo-free. A lot of investors ask us whether we're going to replace chemotherapy, whether we're going to replace ADC.
To the contrary, we may be thinking of using our ATTC in combination with chemotherapy and still be tolerable in the earlier line setting. That will expand our reach to even more patients. I guess the second thing that I want to bring up, and maybe I'm jumping ahead, Clara, like one of the things that we're very excited is that, you know, over the last 20-30 years, you have small molecule drugs or the science behind small molecule drugs. Some of these very good ideas are very effective in curing tumor cells, but they never make it to the marketplace because they are or they were too toxic, right? They were too toxic. Small molecule actually is notoriously having very narrow therapeutic windows. You can see some of these pathways struggling to come up with small molecule drug.
Like this PI3K pathway is basically the very first ATTC molecule we are working on. 50% of the solid tumor actually has this regulated PI3K pathway. It's only until recently that you start to see some phase three trial data from some of our competitors in this space. If we can put this very toxic small molecule drug onto our ATTC platform, which is a targeted platform, then we kind of don't mind the toxicity because that construct is going to be just going to the destination tumor cells and have as little off-target toxicity as possible. The exciting thing, very exciting thing for HUTCHMED is that, you know, we can now bring back our small molecule expertise last 20 years. A lot of these small molecule drugs, which we may have given up to become a real commercial drug, to put it on this platform.
It may not be just our small molecule drug, but, you know, throughout the scientific community, there are so many others, as you can see, like the RAS and the others that also struggle to become a drug. Maybe if put on the ATTC platform, then it starts to make sense.
Maybe take a step back. You've mentioned a lot about the safety and the frontline combinability. How important is it for your molecules to have single-agent efficacy versus maybe it's optimal safety for a combination in frontline?
Yeah, so far, you know, we have some animal data, and this may not answer fully your question, Clara, but the chart you see at the back, you know, one on the left-hand side is kind of tumor size reduction, which is kind of the efficacy. On the right-hand side is the weight of the mice, which is kind of proxy to safety. You can see that the line, the lowest line, which is the darkest blue line, is our molecule, right? Compare that against that purple line, which is still taking that large molecule, the transductamab, and the small molecule drug, this, you know, PEM molecule into the body, but kind of separately, not conjugated together. You can see the difference. Even though you're taking the same similar content of material into the animal body, but the efficacy of that conjugated is much better.
The reasoning is very simple because they go more directly to the destination site. The similar dosage can have a bigger effect if they are all very targeted to the targeted tumors, right? The right-hand side is also similar in terms of the safety that you can see that if you take the two things separately, the purple line, then you have the weight reduction, whereas our blue line basically has a flat weight because, again, there is no small toxic small molecule roaming freely, you know, in the body to cause the toxicity. This is kind of the concept that hopefully, you know, when we do this by itself, it is less toxic. If you add on to maybe potential chemo, it may be still potentially tolerable to the patients.
Got it. Maybe before we move on to the next for Zhengguo, let's just talk about the development plan and the timeline for the first candidate. Are you looking for any partnership opportunity for this one?
Yeah, definitely for the partnership opportunities because I think for most of the market, this platform is like zero value in our stock price, partly because we have not had human data yet, right? So it is just animal data. But we start to see very strong interest from multinational pharma, you know, even at this preclinical stage. We are working on that, but, you know, we are patient. We do not know the timing. If we have human data, maybe like towards the end of next year, of course, the evaluation will be better. If someone is going to come in early, we are also quite open-minded. The key thing is potential partnership. Hopefully, it will bring us two things. Number one is validation by multinational pharma that this global-first ATTC is something that is of good value.
Number two is, I guess, more for the capital market that if one of these agreements can result in a certain dollar amount of upfront payment, then we have many more. We have many more upcoming. Then people can start to get a sense of what this can be potentially worth to the company when, you know, at this stage, I think it's basically zero in our stock prices. The other thing is that for the clinical strategy, I think in contrast to our history, we are going to be a little bit more aggressive. This is kind of our design at this stage, some of these proof of concept trial. As you can see, we are not just going into the second, third line, but we are also moving into the first line, in this case, in combination with chemo at the outright.
We are also looking at HER2-low, right? Which, of course, is even a bigger market. I think the landscape is increasingly competitive and, you know, HUTCHMED is also changing to become even more fast-paced to be competitive with our peers.
Got it. Let's talk about Fruquintinib, which is, you know, definitely a very important part of your global expansion. You have this global partnership with Takeda, and the drug was approved in 2023 in November for metastatic colorectal cancer. Maybe just talk to us about, you know, how's the launch going so far and what kind of feedback you're hearing from prescribers and payers.
Yeah, so it has been doing very well. And then, you know, Takeda has done a great job in launching this product in the U.S. and around the world. I think, you know, it's one of the best-selling oncology drugs within Takeda oncology portfolio. So we are very happy. I think going forward, the incremental growth in the upcoming year may also be more from Europe and Japan. You know, if you remember Europe, we got approval 2024, but, you know, European insurance coverage is country by country. That's continuing to be, you know, Takeda working on that one. I think first half this year, we also got included in the U.K. NHS program. We look forward to having more insurance coverage in different countries. Japan, the launch is fantastic.
Japan has a colorectal demographic basically the same size as the U.S. markets, of course, at a much lower selling price, but it's still a very sizable market. I believe Takeda also has some home country advantage in that area. That, I think, you know, will be continuing to be the realm of this product. I think the area we hope and we should continue to get better is in the third line settings. I think in the fourth line, we've done very well. In the third line setting, we have some established players out there. We need to, you know, fight harder in that third line settings. Back in China, we actually have two, well, one approved indication called endometrial cancer to the targeted indication for fruquintinib.
The next one we're working on is kidney cancer, second-line kidney cancer, which has reported very impressive results in the ESMO conference and is under review by the China authorities. Next year, or maybe second half next year, this drug may have three approved indications potentially in China. That should continue to drive the growth of this product in China.
What are the key timeline and milestones that investors should be kind of watching for fruquintinib in China and globally?
I think for overseas, it will be basically sales threshold that will hit the next milestone. Unfortunately, we haven't disclosed the exact level, but we look forward to hitting them in coming years. For China, it will be, I think, hopefully around the middle part of next year, we will get the kidney second-line cancer approval. So that's kind of the timeline for fruquintinib.
Okay. And then beyond Takeda's partnership, you also have another global partnership with AstraZeneca for several latent NIP. You recently just presented phase two global trial data in the second line EGFR mutant non-small cell lung cancer at ELCC. Maybe just walk through us the key highlights there and how the global phase three study has been going.
Yeah, so this is another drug we have been very excited for a long time. And for those who follow us, you know, they have heard about this for a long, long time. So finally, I think for the U.S. market, it's getting there. You know, the trial that AstraZeneca is running called SEPHRON, they have completed recruitment a few weeks ago. And then you count another, you know, eight to nine months then to the readout roughly in the first half next year. Now, beyond that, of course, depending on the quality of data, it will aim for U.S. filing. So if I have to guess, you know, sometime in 2027 would be the potential approval and launch in the U.S. Now, this remains the only one around the world which focuses specifically on c-Met-amplified patients. There are definitely an increasing number of different modalities covering second-line lung cancer.
A lot of doctors are saying that this is getting very complicated. We remain the only one targeting c-Met patients. I think this is very important because c-Met patients have definitely worse prognosis than, you know, c-Met-negative, very, very substantial worse prognosis. In the past, when you have no drug approved specifically for this group of patients, then, you know, there are many, many different choices. If we get good data out and if we get approved, I think this is the only one. I think this will be a very important message to the doctors. The second thing, of course, is our drug will be used in combination with AstraZeneca blockbuster Tagrisso or savolitinib. Our partner is AstraZeneca. This actually makes perfect sense. If they sell more of this combination, they also sell more of Tagrisso.
I think the interest is very aligned on this one. Yeah, we wait for the data to come out. You know, personally, I think, you know, we have quite a good confidence. Remember the control group, the control arm is chemotherapy. I think it's a good chance that we can deliver good performance.
We just quickly touched on the market opportunity in the U.S. versus China. You also just had the China NMPA approval in June this year. Maybe how large is that opportunity?
Again, need to be a little bit careful because AstraZeneca has not given any guidance. If we just do the total, the TAM, the total addressable market, you know, calculated by the prevalence of, you know, EGFR positive and c-Met over-amplified, it is roughly about $1 billion type of total market in the U.S. It is also roughly about $1 billion in China. They are similar because despite having more patients in China, but likely the selling price is going to be much lower in China. So roughly $1 billion each. This has not counted something that we are working in China only, which is the first line indication. This next trial called Zhenping, which we also had completed recruitment, of course, the follow-up, which will be much longer.
If this also comes out to be successful, the market size will be bigger than what I've just mentioned.
Maybe for the last minute or two, let's just talk about the SYK inhibitor you have for ITP. I think last time you mentioned generating more stability data for NDA submission. Just tell us how is the process going and, you know, what does the updated timeline look like for this?
Yeah, so this is one that, you know, we are very happy with the clinical data. As you may know, this condition called ITP, where your body cells destroy your blood platelets, there are some new modalities coming up and got approved recently in the BDK space, in the FCRN space, right? But most of them can only achieve a durable response rate of around 25-35%. We have 50%. So we are, you know, at quite a good competitive advantage versus even the new modalities under development or recently launched. We got a little bit of setback in manufacturing with the CMC, you know, late last year, which now kind of reset the clock a little bit to resubmitting the data to the Chinese authorities in the first half next year.
If everything goes smoothly after that, then we will be targeting a China approval and launch sometime in 2027. We look forward to this one because this is our, you know, very first and so far the only one autoimmune molecule that we are working on. Again, like this is also more a chronic disease. This will open up a new potential market for us. Again, this will help to support our China-based earnings and growth in the next few years.
Maybe for the last 30 seconds, I know we're running out of time, but you do have very broad pipeline products. Is there anything else you would like to highlight and maybe any updated thoughts on BD activities as well?
Yeah, I think in the next 12 months, we continue to put increasing focus on our ATTC platform. I mean, I like to sometimes paint the picture of HUTCHMED as having a very late-stage commercialized stable products and earnings and strong balance sheet. And then we have this early-stage preclinical global-first platform ATTC. In terms of excitement, I think the ATTC part may generate more so in the next 12 months.
Okay, perfect. That concludes our discussion here. Thanks, everybody, for tuning in.
Thank you. Thank you, everyone. Thank you.