Okay, good morning. We'll continue with the next session. I'm Paul Choi, and I cover the SMID cap biotechnology sector here at the firm. It's my pleasure to welcome HUTCHMED, and to my immediate left is Dr. Michael Shi, and to the far end is David Ng with IR. What we'll do maybe is start with Michael and David.
Maybe if you could just for investors who may be unfamiliar with HUTCHMED, provide an overview, particularly since you guys primarily focus on the China market, and so people may not be necessarily as familiar with your company. So if you could just maybe describe your key products and key markets, that'd be great.
Yep. Thank you, Paul, for inviting us. Yeah, so I'm Michael Shi. I'm the R&D head and CMO for HUTCHMED. And I think HUTCHMED, for people who are not so familiar, is headquartered in Hong Kong and also have a pretty integrated, you know, research, discovery, and commercialization and marketing in China.
And we have about 2,000 employees. And globally, we have a strong clinical developer team. So I think for the past two years, we're really put up on the global stage. In China, as Paul said, we have three marketed products: savolitinib, fruquintinib, and also the surufatinib. It's all marketed in GI oncology, in colorectal cancer, and neuroendocrine tumor, and MET exon 14, non-small cell lung cancer. I think for the past two years, really, we have some very strong global development, right?
In particular, last year, we had a first product approved in the US with fruquintinib, Fruzaqla, which is licensed to Takeda, which is approved in third-line colorectal cancer. We are expecting the EU approval and Japan approval later this year. I think the next stage is really important and significant for the company.
The milestone is our second innovative product, Savolitinib, the MET inhibitor, even though it is approved in China in MET exon 14, but through our global partner, AstraZeneca, we are expecting this later stage clinical trial to have a completed readout, the SAVANNAH trial, later this year. Hopefully, if the data is positive, we will have a second innovative product to file an NDA in the US.
Next, I think the next one is our hematology product, particularly one of the SYK inhibitors will be presented at the upcoming EHA presentation with immune thrombocytopenia. We have a strong readout in China, phase three. We have our presentation this Friday. That will also put out in the second wave of product in the global development. We're very excited about this. Yeah.
Great. People don't realize this maybe, or maybe unaware, but last November, you got, as you mentioned, Fruzaqla approved here. And I believe that's just the third China-developed drug after Legend's Carvykti and Brukinza from BeiGene to be approved in the US. So it's quite a significant milestone here.
It's approved for later line CRC. So maybe can you describe what's been happening with the launch today? I know it's early days and it's only been a couple of quarters here, but maybe you could talk about the commercial progress to date with your partner, Takeda.
Yeah. And maybe just let me describe a little bit about this product. Fruzaqla is pretty much a late generation, very specific VEGF inhibitor. It hits very specifically the VEGF receptor one, two, and three, unlike other products. So it has a very strong potency and very good safety profile because of the specificity. And we have two pivotal trials. One is in China in the third-line colorectal cancer and called FRESCO.
And in the international, we have FRESCO-2, which is also shown in the later-line colorectal cancer setting, very strong overall survival benefits. So even though it's a VEGF inhibitor, but we think it's not a new target, but the differentiation, the high specificity, and the safety profile really puts it out on the global stage.
It was approved based on two pivotal trials in the third-line colorectal cancer, you know. We work with our Takeda partner to really commercialize the product. So Takeda is actually the, you know, taking the global rights for commercialization. So David can comment about the commercial and for sure.
Yeah.
So we have done quite, quite well so far. I mean, it's still early days. So we caution, you know, investors to maybe look at more quarters of data before doing any extrapolation. But like first quarter is north of $50 million of sales in just the US. Very nice uptake. And I think, you know, we continue to see a lot of good, you know, acceptance by the doctors on the ground.
I think it's also worth mentioning that if, if we just look at the first, calendar Q1 sales of like the global, I guess right now we have like three major innovative drugs selling in the colorectal space. The pie has got, gotten bigger. If you compare like a year ago when there you only have like two major drugs innovative, out there, the pie actually has expanded by 30%.
So I think, you know, on one hand, we are definitely taking some market share from some of the competing products, but the whole pie is also expanding. The duration of treatment has expanded quite significantly too, right? Because if you look at the previous drugs, you know, the PFS is much shorter and now it is longer.
So we continue to see not just, you know, gaining healthy market share, but also seeing like more colorectal cancer. Maybe previously they were just using regorafenib chemotherapy in the third-line scenario, but they are now using, you know, the more innovative drugs. So we continue to be quite positive on that one.
Okay, great. If memory serves, you got a $400 million upfront from your partner, Takeda, which I believe ranked in the top 10 of licensing upfronts last year for that arrangement. So I guess the question here is, you know, you got a very large milestone, but based on your ongoing partnership with Takeda, you know, how do you think about the role of the partnership model for future launches in the U.S., you know, particularly, you know, in oncology, right? You know, what are the key considerations here versus going alone?
Yeah. So I think, you know, Takeda has really set up a very good collaboration. So I think we are very collaborative. I think really utilizing MNC for the product launch and commercialization is really taking advantage of their strength in the global marketing, which HUTCHMED doesn't have, right? So from the, you know, at least I was at the ASCO last week, we see a very strong enthusiasm in the marketplace about the Fruzaqla and the physicians. Takeda put on a good show.
Their education centers are talking about fruquintinib, talking about the global data. We see a large penetration of the, you know, their MSL team, their commercial team really have a very good excitement generated, even their booth, the whole screen looking at the product launch. It's actually quite unique and very eye-catching just from my perspective.
I think we have set up a very good example for commercialization, with the global partner and really helping us to leverage the R&D manufacturer and the China experience, right? The other example, we're also taking our second product as the MET inhibitor, savolitinib. It's also have an early stage partnership with AstraZeneca.
We think these really set us up, you know, in a good foundation, to really leverage their strengths to not only commercialization, but the future global development, taking on the invest further investment for that. As you also mentioned, thinking about, we think also is a de-risk approach for commercialization. Probably sometimes realizing the China-based our geopolitical risk to some extent. For the short term, we think this is the our licensing and partnership will be our approach for the global commercialization.
Sure. I wanna circle back towards geopolitical risks, maybe a little bit towards the end, but stick with fruquintinib for now in terms of China where you've done really well commercially, particularly since, you know, taking, reworking the rights that you previously had with Eli Lilly there in terms of the commercial.
So can you maybe talk a little bit about where you could go beyond in terms of CRC, in terms of potential label expansion and, you know, how do you size up, you know, key opportunities? I think first and foremost probably is the gastric opportunity there in China.
Yeah. Thank you, Paul. Yeah. So, we are very excited about the gastric cancer opportunity. It's a huge patient population in the second line setting. So the trial we have conducted is a China phase three trial, fruquintinib plus paclitaxel versus paclitaxel. You know, the data was actually reported earlier this year at the ASCO plenary, and you know, last week at the ASCO plenary we provided an update on the data with our presentation. And it also has a concurrent publication in Nature Medicine.
We are very excited about the data, not only shows very robust, you know, it's a dual primary endpoint with a progression-free survival and overall survival. For PFS side, we see significant improvement of the progression-free survival, almost doubled with an HR of 0.57.
We also see very robust overall response rate, 42% in the treatment arm versus placebo up to 20%. The overall survival also we have seen pretty much along all the second line data, 9.6 months overall survival. It's the longest OS benefit we have seen for the second line gastric cancer treatment.
We also published the you know post-therapy treatment imbalance lead to the you know significant difference of the imbalance of the post-treatment lead to the OS doesn't really achieve the clinical I mean statistical significance. Still we see the benefit. We're very excited about the data. The data is already you know supplied the analysis to the CDE. We expect the decision Q3 this year. This will be an important area with high unmet need.
The other area is the combination because I mentioned specificity of the fruquintinib against VEGF receptor. It's a very good partner with other immunotherapy, chemotherapy like what we see in the Fruzaqla therapy. The next one we also present our pivotal phase two data, fruquintinib plus sintilimab, in second-line endometrial cancer.
We observed very robust overall response rate. So, OS, overall response rate 35% in this treatment setting. We also submitted the NDA. This is the clinical trial design was already agreed upon with the CDE. We submitted the application. NDA was accepted in April. We expect that decision by end of this year. Along with the other label expansion, we also see a combination with the FU with the sintilimab combination PD-1 in the renal cancer. This is the second-line versus axitinib or everolimus.
The patients were, I mean, recruitment was completed last year. We are waiting for the event later this year. It is event-driven. So hopefully, if the data is positive, we're gonna file NDA next year so that will really further expand the label for fruquintinib in China. And a lot of these data also kind of, we're in discussion with partner to see if there are any global opportunity for fruquintinib in a global setting to further maximize the value for fruquintinib.
Can you just remind me, in China, second line standard of care in renal is still Axitinib. Is that correct?
Yes.
Okay. Even though in other markets there's PD-1 plus Cabozantinib or PD-1 plus other?
It has no immunotherapy, combination has been approved in China. That's why we agreed upon with this clinical trial design with the CDE. Yeah.
Okay. Very good. I wanna maybe pivot to Savolitinib and lung, where your partner AstraZeneca obviously has a very large, you know, blockbuster EGFR franchise with their Tagrisso drug.
And, you know, you and your partner have indicated that you're planning to potentially file an NDA by year-end based on the SAVANNAH data in a second-line study, which is global, not just China-based. And that could come by year-end. Can you maybe remind us first of all how much of the MET-positive population in second-line lung this could potentially address? And we can start with that.
Yes. So, you know, just on top of that, I think savolitinib was actually approved in China, in a very specific indication in the MET exon 14 mutated patient. So, you know, in the approved indication, you know, in the US, we know the capmatinib, tepotinib also approved, in MET exon 14, but it's actually very representative of a small patient population because MET exon 14 is a key driver mutation in non-small cell lung cancer, but it's only accounts for about 1%-2% of patient population.
So it's a relatively small, kind of a market. And for the global development plan, AZ and HUTCHMED is taking is addressing the MET aberration, right? Overexpression, the amplification, that really accounts for a strong resistance to VEGF TKI.
So in the global setting, in the Western patient population, MET, EGFR, MET mutation, EGFR mutation is actually quite large, account for 10%-15% of the patient population. In the Asian patient cohort, it's just much higher. It's about 40% the Asian patients have EGFR driven mutation.
So that lead to non-small cell lung cancer. So sooner or later, even though you have first generation, second generation, third generation EGFR TKI, but regardless, the patient eventually progress from those EGFR TKI. So one of the major mechanism for EGFR is the MET amplification or overexpression.
That you know from the previous SAVANNAH trial we published is account about 30, over 30% of the patient population. So that actually addressing a even larger patient population. So the SAVANNAH trial is really taking this approach in the second-line EGFR-mutated resistant patient population.
The combo with savolitinib and the Tagrisso, really significant, extend the PFS and had a higher response rate. So the overall response rate from the previous, you know, the exploratory stage, the SAVANNAH trial we published, it is about 50%. So 52% overall response rate. And that really lead to the development for this SAVANNAH trial to really addressing this patient population.
So if the data holds, right, the primary endpoint is overall response rate. It reproduced the previous result. AstraZeneca is gonna lead the NDA submission later this year. That's, you know, our partner's timeline. And we really hope that will also, you know, after the Fruzaqla, it put our HUTCHMED innovation to the global stage the second time. So we're really excited about this opportunity. Yeah.
Okay. Great. You mentioned this earlier that sales of like Pemazyre and other MET drugs, you know, are addressing only a small part of the market and sales of the approved inhibitors while small, you know, haven't quite hit blockbuster status yet.
So how do you think you and AstraZeneca maybe can grow the market here? Is this sort of a lack of information among clinicians? Is it just poor treatment options, poor patient behavior? What sort of factors can grow the market here in the MET space?
Yes. Right. So actually, you know, I think that's really under, you know, the MET amplification EGFR resistance is really the kind of a not yet present in setting, data before. But you know, even though it was through AstraZeneca development and our development, we I think people are realizing the MET amplification is an important resistance mechanism, but there's just really AZ and HUTCHMED is really in the early pack of lead in this indication.
So certainly the physician education, certainly the additional data, you know, I think hopefully the publication coming out from this study, SAVANNAH pivotal trial, will really further awareness, set us apart from other competition in this field. And even for the MET exon 14 mutated patient, we also at HUTCHMED we have this China registration trial before. We also have a line expansion indication.
So we already completed not only the second, third line, which is already approved indication in MET exon 14 in China. We also have our first line readout published earlier this year at the ELCC, which has also set us apart from the other competitor in the first line setting. You know, we have observed very long, you know, high response rate, over 60% ORR, in the first line MET exon 14 mutated patients.
And also the overall, I mean, the overall survival has now been reached the PFS above 13 months. So it is really significant in MET driven disease area. So we already submitted the first line label expansion in China. Hopefully we will also get approval next year, early next year. And because of that data, we also have a full approval in the second, third line setting.
Mm-hmm.
And the first line setting. That will certainly grow the market, not only for the MET exon 14 mutation, but also the EGFR resistant, you know, non-small cell lung cancer setting. Yeah.
Okay. Great. I wanna switch gears and maybe talk about what I think is your most exciting but maybe least known asset, which is sovleplenib in ITP. You've recently presented some data on it and you have more data coming up here at EHA. But I think the data are really impressive.
You know, when you think about standard of care here is largely steroid treatment and things like that. And your duration of response looks to be pretty long as well too. So can you maybe help us contextualize the data, what this means in the disease area of ITP and what next steps for the program are?
Yep. Yeah. Thank you, Paul. This is, you know, this is more exciting data. We're actually presenting the data on Friday, at EHA in Madrid. So the abstract has had an early release. But the funny thing is, Paul, the EHA still informs us that the data is kind of at the embargo stage.
But the abstract is all that we can talk about is absolutely, you know, fascinating as what you point out because the duration of response for this, in this heavily pretreated ITP patient population. 'Cause the traditional, I mean, the trial was conducted in the patients, 188 patients, two to one randomization, ESLIM-01 phase 3 trial in China. And we have observed overall response rate of 48%. So our initial phase 1 proof of concept study was about 40% ORR.
But this, the phase three data is even far exceed our expectation, with the durable overall response rate, which is the primary endpoint. And the placebo is zero. So that really spell out how clean, how robust the data will be.
Just gave you a context, the SYK inhibitor, which is in the US and EU, there's approved the medication, is a Fostamatinib in the similar line setting, with a less, TPO-RA pretreated patient. So, in this setting, the TPO, TPO-RA is the primary second line. After steroid, TPO, TPO-RA are primary the second line setting. So for the Fostamatinib data, even it's a good, approved, the overall response rate is 18%. Okay. So same class.
What we believe, not only we have a very specific SYK inhibition, but also, similarly less like fruquintinib, because the unique and the specific inhibition leads not only to increase the efficacy, but also decrease the undesired off-target toxicity. What fascinates us about this data in this patient population, heavily pretreated, placebo response is zero, right? You see the average prior line of therapy is four lines of therapy.
And 75% of the patients have been previously treated with TPO or TPO-RA. Some of them have multiple TPO-RA treatments. We're gonna also present the subgroup analysis, you know, in EHA with the two posters. The data really show this compound is clearly highly potent and, you know, it also does not have the prior therapy, which is the other mechanism, TPO-RA.
Primary mechanism is stimulate the platelet production to bone marrow. The SYK inhibition is primarily. It has a dual mechanism. One is the inhibitor macrophage destroy the platelet, which is due to the autoantibody production.
And also they inhibit the B cells production of autoantibody production. So these two mechanism addressing the fundamental of the immune thrombocytopenia. It also does not have the TPO-RA has the more severe toxicity, which is the platelet overshoot and lead to high thromboembolic event. So we see zero thromboembolic event in the phase 3 trial.
That's great.
Also, we're gonna present the patient-reported outcome, the improvement of physical health. Some of these data also at the EHA NET later this week.
Okay.
Yeah.
Great. I wanna turn maybe just to regulatory next steps, for the program, maybe starting with China, where you did complete the phase three, and maybe just sort of, you know, what's happening there potentially with a priority review or accelerated review there. And then, in terms of the global opportunity for ITP, can you maybe just comment on where you are with regards to alignment with the FDA and other regulatory agencies outside of China on a potential pivotal trial here?
Yes. So we communicate and discuss with the FDA about the global development plan. So we are already starting international phase one trial to really looking at the dose escalation, dose optimization for this trial. So the design has been agreed and with FDA. We're already starting this trial.
We're opened a few centers already in the United States with the first patient coming, you know, pretty shortly. And internationally, we think, you know, this is really still, you know, because the compelling data, we have a lot of enthusiasm for our investigators in the United States, in EU, Australia. And so the global development will kick in pretty shortly.
And also, future there has huge opportunity, I think, for the global development, not only in the previously pretreated setting because the safety profile, the uniqueness, the specificity of the SYK inhibitor. You also have a potential to move early line, even in the combination setting. So that's what we believe this molecule has a lot of potential because truly has this best-in-class potential for global development.
Okay. Great. I wanna maybe change tacks one more time and maybe turn to a bit of a sensitive subject, but maybe David, if you could speak to, you know, what has been, you know, seemingly like a more hostile stance of the U.S. government towards China biotechs and, you know, potential exposure to sensitive technologies.
So, can you maybe talk about what strategies, if any, you know, HUTCHMED is taking to navigate this environment, the current environment, and maybe, you know, what do you see as either potential headwinds or, or tailwinds for, for China biotechs such as, such as HUTCHMED?
Sure. I think it's a very, very topical issue, last few months and on a lot of investors' mind. I think for HUTCHMED, as you know, we focus on innovative drugs, right? We focus on the science. And I think since day one, we have been aspiring to not just be a China biotech, but, you know, one that can have global commercialization.
And, you know, we have delivered that, right? You know, not just through, you know, partnership and R&D stage, but also at the commercialization stage. I think like when we did the deal with Takeda, two years ago, right? Almost two years ago, you know, part of that, of course, is for the commercial reason, right? We got huge financial upfront. We got, you know, royalty, with a lot of risk. So that's kind of the de-risking part that Mike mentioned.
But now, you know, at this stage, there may be another de-risking part that, you know, we do have an MNC, you know, on the label of the bottle, it's Takeda. If you look at the approval labeling, it's Takeda. You know, so that actually may de-risk a little bit, you know, versus we doing it all by ourselves.
But the other thing, of course, is, I think at the end of the day, it's still a product which has much more compelling data than some of our competitors. I think that truly is what we can control. I mean, like a lot of the other things like the geopolitical risk or any other legislation that may come, it's not controlled by us, right? You know, we can just go with the flow.
But, you know, the thing we can continue to focus on is, you know, we have good drug candidates. I think as you may have noticed that, you know, recent days you have some seen high profile news about some company not having very good manufacturing standard, right? You know, we are, again, like we are very proud, that, you know, we pass all the manufacturing inspection, all the clinical site inspection, with relatively, you know, almost no, no issues at all.
And I think that is not something easy to say for a lot of our peers. So those, those are the things that we, we continue to focus. Like, I think, you know, I, I always remind people that we are a, more than 20-year-old company. You know, we've went through a lot of ups and down.
We went through a lot of the things that takes time to learn the know-how, right? Not just in terms of clinical, but also manufacturing. So we think that this should equip us, further down the road, not just for the China market, but also for the global market. There still continue to be these kind of uncertainty, but we focus on what we can do, do best, right? So, you know, for our next product, next potential US product, you know, savolitinib, we already have our partner in place.
For our next, you know, SYK inhibitor, we definitely will continue to seek out, capable partners, multinational, big biotech to be our, commercial collaborators. So I think that's, that's kind of, the, the answer. I think the other thing, of course, is science is still science, right? If you have a drug that can extend the PFS by 50% or 100%, I think that is still much more important than any other geopolitical risk.
Okay. Great. You're also like talking about, you know, pivoting to break even and profitability in 2025. I guess as you think about your product cadence and your OpEx trajectory over the next few years, you know, maybe can you just comment briefly on, you know, how you think you're progressing against that goal to be break even or profitable? And then just, you know, how other factors are coming into that.
Sure. So at the end of last year, we have very, you know, relatively quite safe balance sheet, you know, over $800 million US cash. And, you know, of course, last year was a profitable year because we have the upfront payment from Takeda. This year we will continue to do our R&D and everything that, you know, but then 2025, we target to break even. It's not one-off break even.
We want to be sustainably growing afterwards. The burn can be mitigated quite nicely. I think, for not just our major shareholder, but also for, you know, future investor shareholder, I think that is something quite important to see not just good product coming out from our company, but a sustainable operation, that can do many other things.
I think it's not just the current pipeline that you should be looking at, but, you know, the, you know, with our, you know, skill set, with our balance sheet, you know, we can do many more other things, you know, in the medium-term future. And I think that is quite key in an uncertain capital market, as we all know these days.
Yeah.
So, and we do also have a new manufacturing plant, recently opened in Shanghai. It's not in full-scale commercial stage yet, you know, in for clinical batch, we can do that. But then, you know, in the next few years, we will enter into the commercial readiness of this, of these manufacturing facilities, which will hopefully also continuously increase our cost synergies, our production margin, should gradually increase with this.
So that's another part of our thinking that is not just at the clinical front or approvals, or regulatory front that we want to be a commercially sustainable and continuously growing company for our shareholders.
Okay. Great. Maybe to close, if you could just remind us, Michael, maybe one top two or three catalysts we should watch for over the near term from HUTCHMED.
Yeah. So, yeah, Paul, this is just kind of a mindset, you know. As mentioned, I think the major catalyst will come from our, you know, R&D side is really the near-term approval, NDAs, right? So first is the indication extension for Fruzaqla, for fruquintinib. We continue to have the GC, the endometrial, the RCC, either at the NDA stage or approval or the NDA submission stage.
And also the savolitinib, we're gonna have a full approval for MET exon 14. And our exciting partnership with AZ will lead to new indication globally, right, for savolitinib for the non-small cell lung cancer with the MET EGFR mutant resistant patient population. That's really the indication expansion for all these existing products. The next is new products coming. We mentioned about a SYK inhibitor, not only in the ITP, but also we have development in the lymphoma.
We also have other autoimmune, you know, disease potential to be developed. The approval for ITP is coming, and also in the EHA, we're gonna show our POC trial for the, you know, warm autoimmune hemolytic anemia.
That's also very robust data. We are very excited about a SYK inhibitor. In China, we also have our in-licensed product, Tazemetostat, EZH2 inhibitor. We're completing this NDA filing later this year. So new product, new indication, it will be the key driver and catalyst for ours to contribute our 2025 commercial breakeven and sustain the growth stage, so it's gonna be exciting for the company.
Great. Okay. We'll have to end it on that note 'cause we're out of time. Thank you very much.
Thank you. Thank you, Paul.
Okay.
Yeah.