All right, great. Hey, everyone. Good afternoon, and welcome to day two of the 2024 Bank of America Healthcare Conference. Thanks for joining this session with HUTCHMED. My name is Alec Stranahan. I'm Vice President and Senior Biotech Analyst covering HUTCHMED here at BofA. And I'm pleased to be joined by Michael Shi, Chief Medical Officer of HUTCHMED, as well as David Ng, Head of IR and Corporate Strategy. I believe that's right. Capital Strategies. My bad. Thanks for being here, guys. Really appreciate it.
Thank you for inviting us.
Yeah.
Thank you.
Great. So I don't know, Michael, do you wanna just run through a little bit of, you know, the most exciting things going on at HUTCHMED right now, you know, what, what you're most focused on? And then we can maybe drill down to the, the different, assets you have.
Yeah. So, yeah, I think since last year, right, Alec, we have making tremendous progress, right? Mainly, FRUZAQLA was approved in the United States for third-line colorectal, CRC, and was, you know, under the priority review, is really I mean, it's really succeed our expectation. And also, last month, we got a European positive opinion, so is absolutely on track for the approval this year. So this is a significant achievement with our partner, Takeda, and as you're here, probably, David can drill down a little bit on the commercial side. It's absolutely exciting, and, and also we have some top-line results on the related with the fruquintinib in life cycle indication development and also some of our new pipeline. We're gonna drill down more about it, particularly upcoming EHA for our SYK inhibitor.
And also, later this year, we also think we have a very good opportunity, as you know, Alec, you know, the savolitinib, AstraZeneca, our partner, has completed the, SAVANNAH, you know, pivotal trial enrollment. We're waiting for the events, hopefully later this year. We're gonna file the second, you know, ex-China, the U.S. NDA. So this is, for the company, we is really enter an exciting year and hoping for the next few years, we're gonna hear more about, our strategy to make a sustainable growth company. Yeah, so absolutely delighted to be here.
All right, great. So definitely a lot of ground to cover, so I want to jump in. But I will mention if anyone from the audience does have a question, feel free just to raise your hand, and a mic will be brought over to you, and you can ask it. But, Mike, Michael, maybe just starting on fruquintinib, recently approved in the U.S. with Takeda, third-line CRC, obviously, most topical right now. Could you maybe quickly remind the audience what's happened with your asset, your Takeda partnership, and, and where we are in terms of the launch?
Yeah. So fruquintinib was originally approved in China for third-line CRC. It was approved six years ago, and now we are actually the market leader in third-line CRC, with 50% of the market share and still continue to grow. It's a strong growth driver for the company. And we also run a successful clinical trial for the FRESCO-2, is actually a fourth-line, you know, CRC, in the global, you know, ex-China market with US, Japan, EU, and Australia. And what we found, the results is as exciting as the third-line CRC. So we were working with you know, Takeda to actually file third-line CRC. FDA accepted. It was actually, it's a very successful regulatory milestone for us.
Not only get approved, you know, the anticipated fourth-line label, but actually we were able to get the third-line CRC label in the U.S. market. So it was quite a successful story from regulatory perspective, and we are very excited about the commercial aspect. The EU approval is already, you know, right on target with the positive opinion. Yeah.
Yeah, fantastic. And I think, you know, Takeda, in their recent quarterly filing, has started breaking out for FRUZAQLA sales, maybe around $50 million for 1Q. You know, how is the launch progressing so far from what you've been seeing with your partner?
Yeah, it was. From our perspective, it is actually quite actually exceeded our expectation because, certainly, you know, in the third-line CRC, this is probably the first time we see a new entity was launched in close to 10 years, right? So it generate a lot of excitement in the physician and the patients. So the uptake, it is pretty successful. David, you want to comment on that?
Yeah. So I think the, as Alec mentioned, the, the Takeda breakdown for the very first time. There's no specific guidance for the full year, but, you know, the, the, the ramp has definitely been very robust, very strong, and we've been monitoring some of the competing products, and, and it does actually imply quite a significant market share, even though it's just the very first full calendar quarter that we are in the market. And from what we heard, right, again, like, the adoption as well as the, the education has been going on quite, quite strongly. So this will definitely become a very strong driver. It's not just in terms of our, I guess, stock sentiment, but also in terms of our fundamentals in the upcoming years.
We, you know, anticipate more to come, especially we have the potential European approval.
... happening maybe in two months' time, and then, you know, Japan approval for later this year. So this overseas sales will continue to be one of the key things that will be supporting our fundamental.
Right, and obviously, having Takeda as your global partner will help with all those geographies. And you know, you mentioned some of the prior therapies or competing therapies. You know, looking at the data, fruquintinib clearly shows prowess over regorafenib in TAS-102, which, you know, seem to be the most notable comps out there. Could you maybe walk us through the strengths of fruquintinib over its competitors and where you see fruquintinib slotting into the metastatic CRC treatment paradigm?
Yeah. So, you know, just a little bit background. Fruquintinib actually was designed to be a very specific VEGF inhibitor. It inhibited VEGF receptor one, two, and three, unlike bevacizumab, but it's the other agent is more VEGF R2. And what we believe has set us apart is really the VEGF receptor R3, because not only involved in the angiogenesis, but also lymphangiogenesis.
Mm.
If you look at the regorafenib, the other anti-VEGF therapy, what we observed is not very effective with patient with liver metastases, which is really common in the CRC patient. So we'll see the patient with liver mass in the FRESCO-2 trial is similarly equally benefited from the fruquintinib treatment. So that's really exciting, kind of a clinical validated this VEGFR3 mechanism of action. And also look in the absolute increase of survival, because in the FRESCO-2, you can see the 2.8-month improvement of OS, really, compared with the regorafenib and TAS-102 is pretty much like a 1-month worth difference.
And also the PFS for the fruquintinib mCRC, we see it at 1.9-month PFS versus, you know, 0.2-0.3-month PFS improvement for regorafenib and TAS-102. That's really even though it is not direct, a head-to-head comparison, you can see the clinical outcome benefit for fruquintinib. And the other part is also related with the specific target inhibition. We don't see this, you know, off-target effect, you know. So if you look at the liver safety is actually quite good. Regorafenib has this, you know, black box for liver toxicity. Fruquintinib doesn't have restriction. We don't have severe myelosuppression like, you know, TAS-102 with the chemotherapy.
Also the hand-foot syndrome is less, and it's the physician and the patient is really thinking it is very highly tolerable. So not only from the safety, efficacy perspective, but also safety, it really set us apart compared with the other competitor. That's why, you know, the market, I mean, the, you know, physician, patients are very excited about this new product launch in the United States. Yeah.
Yeah. Very differentiated product profile, which, you know, could be directly feeding into the uptake we've seen so far to date, right? You also have a few other possible areas of label expansion. You know, you've presented data that shows potential to move to first-line CRC as well, but you also have second-line gastric cancer, NDA under review, as well as in combination with sintilimab for advanced endometrial cancer in China. Maybe walk us through the potential in these other treatment settings and framing around time to approval.
Yeah. So this is again, you know, related to this, safety profile for fruquintinib. We know. We found from the early studies, we find is a, you know, is a very good, you know, safety profile combined with other chemotherapy, immunotherapy. That's how this, you know, new indication expansion was based on the, you know, clinical parts. So for example, for the gastric cancer, you know, with the FRUTIGA trial is a China second-line, combination with paclitaxel. So we did have the top-line result reported February sixth ASCO plenary expansion presentation. Really showed this, you know, highly robust PFS improvement, double the PFS, compared with placebo arm.
And the overall survival, we do see the numerical increase, although from the trial design perspective, it's a dual primary endpoint. If you had either PFS or an OS, is considered positive trial. We do see the post-hoc analysis, you know, there's a imbalance of the post-treatment arm, you know, compared with the fruquintinib plus paclitaxel, compared with paclitaxel. We do see the placebo arm have a higher, like a 20% of the difference, higher post-treatment therapy, which probably explain, is complicated OS explanation. But from the trial perspective, we see the longest, even compared with the RAINBOW- Asia. RAINBOW trial is clearly showed that 9.2 month OS, which is the published data, is the longest OS data in the gastric cancer.
So there will be a subsequent additional analysis, which also selected at the oral presentation at the ASCO next month. And also the main full manuscript will be published online simultaneously in Nature Medicine. So it's really exciting data. From our perspective, the NDA has been accepted by NMPA. We're continuing to provide more analysis, and we expected this reaching the decision point by Q3 this year. And also, there are a few other indication you mentioned in the fruquintinib sintilimab in the urothelial cancer second-line setting. We also reached the positive endpoint. This is a single-arm registration trial via pMMR status, and the application has been accepted by NMPA. We're expecting the decision somewhere towards the later part of this year or early next year.
Also, there's another sintilimab combo trial in second-line renal cell carcinoma. So that's also based on the very positive phase II data. We have this randomized phase III study versus an axitinib or everolimus in the second-line setting. The trial is fully recruited. It's event-driven. We're waiting, kind of anticipated the readout may be end of this year, and then if positive, we'll file NDA. So there are quite some lifecycle indications to fully expand, and we hope to really maximize the value for fruquintinib. Yeah.
Yeah. No, that was a great summary. I want to jump now to savolitinib, and I, I'd say probably most prominent focus here is the savo Tagrisso combo.
Yes.
Savannah, which I believe is expected later this year, followed by an NDA submission. This is your AstraZeneca partnered program. You know, could you maybe walk us through the rationale for going after the combo first and what we should be looking for in the readout?
Yeah. So the, you know, the MET amplification is actually quite common in the EGFR resistant, non-small cell lung cancer. That's what we all, you know, looking at the first stage of the SAVANNAH trial, we're really looking at the patients with the MET amplification responds very well, even those in patients progress on Tagrisso have a high response rate. So savo plus Tagrisso achieved an over response rate about 50%, and with the median PFS over seven month. So, that's pretty much the rationale for the SAVANNAH registration, trial. So it has been, communicated and discussed with U.S. FDA about the regulatory path with the SAVANNAH. A- AZ is a fully recruited patient, by February.
So if looking the events driven, so if we anticipate, repeat over some months, seven months PFS data, so we anticipate later this year, we'll have the top line readout. Hopefully, it's gonna repeat or even exceed our expectation. That will put a second China innovation to the global stage approval. So it's exciting time for us, again, to bring more innovative molecule drug to register the globally, to benefit patient globally. Yeah.
Right. And obviously, having AstraZeneca as a partner, given the strong uptake for Tagrisso, has really entrenched itself as a standard of care. Like, that's probably the ideal partner-
Yes.
You would want in this setting. You know, you mentioned the U.S. expansion of savolitinib, but you also have SACHI and SANOVO phase IIIs ongoing in China. You know, how do these studies feed into your longer-term vision for savolitinib?
Yeah. So this is absolutely important for us because, as you know, the EGFR mutated patient is actually highly prevalent in Asia. So 40% of the Chinese patients is EGFR positive patients. So, you know, sooner or later, right, is the data show they're gonna progress on the, even the third-generation TKI. So that really representing is a big market for us. So there are two parts with: one, the SACHI is a pure second-line setting, with MET-amplified patients. What we see, if the SACHI data, you know, is gonna have a faster readout, so, compare with the, the global SAVANNAH trial AZ is running. So we think we have the opportunity to capture the earlier approval in the EGFR resistance setting, so earlier to commercialize in China, which is a really big market.
And the SANOVO is the first-line setting, is gonna, you know, addressing the MET positive patient in the frontline setting has a high, long durability. That's also important to prevent the, you know, EGFR resistance. So both trial, we have very high hope, you know, is gonna, you know, beyond this and at some 14 mutated patient, is gonna capture a huge market-
Yeah.
in China.
Fantastic. Maybe moving to sovleplenib, and this is kind of leading the charge from your wave two of your pipeline. It's a SYK inhibitor, a very interesting target. The NDA for primary ITP was recently accepted and granted priority review in China. Maybe walk us through the ITP data we've seen so far from the phase III data readout plan, and what timing could look like for an approval here.
Yeah. So I think the sovleplenib one is a randomized phase III trial in the second plus line setting, you know, is a China registration study. That was actually based on the phase Ib clinical trial we did before. The unique feature for the SYK as a target is really important for ITP, because if you look at the traditional ITP therapy is either addressing the platelet production or prevention that destroy the platelet by phagocytes.
Mm.
So, I think the SYK is actually sets us apart, because they not only work on the, you know, blocking the pathway, prevent the macrophage eat up the platelet, but it's also addressing some of the fundamental of the immune disease pathogenesis. 'Cause, you know, the SYK is also expressed in the B lymphocytes, which is really the fundamental is a dysregulation and leading to high production of autoantibody and recognized by the platelet and then lead to the destruction. So not only the inhibiting the SYK can prevent the phagocytosis, also reduce the production of autoantibody. So that's why we think it's a very it's an ideal target for addressing the ITP indication. So the phase 1b data we did is a more dose optimization study.
We select the 300 milligram QD as the, you know, phase III study. So phase 1B study is absolutely set us apart from all the conventional therapy, 'cause we observe, you know, in the second line, plus patient population, most of the patient is actually progressed on all the available, you know, ITP therapy, including TPO-RA, steroids, and all the other medication. So what we found, the durable overall response rate is actually pretty high, it's 40%.
Mm.
That, you know, just as a reference, you know, the Rigel fostamatinib was approved globally for the ITP, but the durable response rate from phase III trial is only 18%. If you look at the other ITP targets for the BTK, we saw there is a burden there, but the overall response, durable overall response rate in the similar patient setting is about 30%. FcRN is only about 20-something%. So this is absolutely exciting days. So, I think with the early preview of the data, 'cause, EHA just released the abstract yesterday, last night, and you can see the top line results published at EHA. So we are absolutely delighted for the landmark phase III trial.
We see even more robust, durable overall response rate is 48%, which is really, really haven't seen that for a long time. So it really excite us. And also, we have another POC trial for another indications, the warm autoimmune hemolytic anemia for sovleplenib, is also selected for an oral presentation. So both abstract has been selected for oral presentation for the EHA next month. We're very excited about. Also, there are some other subgroup analysis and also the lymphoma phase 1 data also being presented at the EHA. So it's gonna be big story for the-
Mm
sovleplenib, the SYK, as a target. Yeah.
Yeah. Great. Definitely looking forward to that data at EHA. And you mentioned your warm autoimmune hemolytic anemia study. So you recently initiated the registration part of this phase II,III study. Could you maybe frame what the market looks like?
Yeah
... in this indication, since, you know, maybe some investors haven't really heard about this one?
Yes. So as you know, mechanism wise, right, it's very similar to ITP, right? Because the autoantibody, you know, targeted red blood cell instead of the, platelet, like in ITP. So it lead to, anemia, you know, it decrease the hemoglobin level. So it has been really a long time. Actually, literally, there's no approved therapy after first line, because the steroid is the, you know, first line treatment. Second line, there's just really no approved the therapy, although Rituxan has been used off label, but it's most of patient will progress of the, you know, in, in this, wAIHA indication. So, the field has been really longing for this, new medication coming in this, in this field, because, it really representing the high unmet medical need.
The patient population size is about half of the ITP patient population, but clearly, this is very high unmet medical needs. So, the data published, you can see, is also a very robust clinical data, raising hemoglobin. So we are really hoping, even from the... It is a phase II,III trial design. Based on the positive phase II, we need to discuss with the NMPA about the registration path, that confirmatory phase III part of early study, just from the enrollment perspective. Even though it's a rare disease, we see very, very high enthusiasm from the PI and the patients. So the recruitment is actually ahead of our schedule. Yeah.
Okay. Oh, very good. Maybe we can turn to financials, and David, I'll, I'll ask this one for you. You guys had $838 million in revenue last year, and you were actually EPS positive, I think, for the first time in recent memory, which, which is great. Maybe walk us through your, your ongoing launches and how you see sales from these assets continuing to grow over the next year or two.
Yeah. We do have a very, I would say, relatively safe cash balance, and we definitely want to keep it that way. Of course, you know, last year we have the upfront payment from Takeda, so that helped quite a bit.
Mm-hmm.
But you know, we also have a you know, in view of the relatively challenging capital market out there, we want to make sure that we are self-sufficient. So, one you know, direction that we're working towards is to be able to break even, hopefully next year, and then sustainable growth beyond that, with our own product, with our own in-house products. The sales of fruquintinib both in China continue to grow, of course, overseas, it's also ramped up quite nicely, help in that aspect. But also the other potential indications that we are working on for fruquintinib in China will also help a little bit. Also next year, we will very likely to have, if the sovleplenib get approved in China, that's a you know, another product for us.
On top of that, we may be also working on some partnership potential for sovleplenib as well.
Mm.
So all these things together, hopefully we will have a strong inflow. Then on the cost side, we have also worked quite hard. We have rationalized our pipeline, focused on the things that will generate the biggest return. So you see that, you know, our expenses size are not actually going up that much in this year or even next year. So, you know, if you, you know, all these things together, I think, you know, we probably doesn't need to have too much external help at this stage.
Mm.
Actually, at the same time, allow us to look at different type of opportunities if it arise.
That's great. You know, I think you ended 2023 with roughly $886 million cash and equivalents. You know, maybe just to wrap things up, we can talk about sort of the catalyst flow over the next year. But, you know, how does this cash balance and, you know, your growing top line set you up to power your pipeline ambitions through the next wave of catalysts?
Well, I think, we have proven to the world that we could do innovative drug from start to finish, not just for China, but also overseas, you know, getting the pivotal registration trial done. That actually, you know, I think help us to attract partners to be able to believe in not just the quality of our product, but also the execution that we have in the clinical phase. So, you know, having the ability also give us more options, like, right? I mean, in the near term, we may want to have maybe multinational to help us to do the, you know, overseas trial.
Mm.
But, you know, further down the road, you know, as we, you know, maybe break even and start to have sustainable growth, we can also entertain different type of strategies. I think, you know, for HUTCHMED, we continue to want to be an innovative company that are able to go overseas. I think that's something that is really setting us apart from a lot of our peers in China. And, you know, we have done it once, and then I think, you know, the second product hopefully will be next year, and then, you know, followed by more further down the road.
Yeah. Right. Great. Fantastic. Well, definitely, a lot to look forward to over the next few months. But I think, with that, we're unfortunately out of time, so we'll have to leave it there. But thanks, Michael and David, for your time and for participating in the conference. Great discussion.
Thank you, Alec.
Thank you.
Thank you.