Good morning, everyone. I'm Paul Choi, and I cover the U.S biotechnology sector here at Goldman Sachs, and it's our pleasure to welcome you, those are here and online, to our conference. Before we begin, we are required to make certain disclosures and public appearances about Goldman Sachs's relationship with the companies that we discuss. Disclosures relate to investment banking relationships, compensation received, or 1% or more ownership. We are prepared to read aloud disclosures for any issuer during the sessions upon your request. However, these disclosures are available in our most recent reports available to you as clients on our firm's portal. In addition, updates to these disclosures are available by ticker on the firm's public website at http://www.gs.com/research/hedge.html. Goldman Sachs agrees to host this conference on the basis that no third-party speaker will provide confidential or material non-public information.
In addition, by attending this conference, you provide Goldman Sachs the right to record and redistribute the conference information. The views of third-party speakers do not necessarily reflect those of Goldman Sachs. Okay. With that, it's my pleasure to welcome Dr. Weiguo Su of HUTCHMED. He's generously come in from overseas to join us here at the conference. We're also joined by Annie Chang in the audience here from the U.S. side. What we'll do is some prepared Q&A with the team. If the audience has any questions or if you want to send questions to us, please feel free to email us, and we'll be happy to read them aloud anonymously.
If we could maybe begin with some, maybe some high-level thoughts on HUTCHMED. There's a lot going on with your company these days. Can you maybe give us the two or three things that, you know, you as a management think that investors should be most focused on as they think about the near-term story for your company, let's say, over the next 12 to 18 months?
Is basically executing in all fronts. On the pipeline, we are focused on basically the late-stage compounds moving through registrations and also on mid-stage compounds, now also, you know, what we call second wave, also reaching registration as well, so preparation for NDA filings. At the same time, progressing our early-stage compounds, now, we call it third wave, into registration studies later this year. Actually, one already in a pivotal study. I think of particular interest perhaps to investors, our ex China effort to move Fruquintinib into registration. Savolitinib hopefully will soon follow as well.
As you all know, we announced Fruquintinib U.S. NDA filing and just granted priority review for the colorectal cancer based on FRESCO-2 results. We are working also very hard on Europe submission and Japan submission as well for Fruquintinib. Savolitinib finally, you know, we are enrolling very fast in the SAVANNAH study, which is a registration intent study. We hope to together with AstraZeneca complete enrollment fairly soon and file next year in the U.S. A major effort outside China and to maximize the value, you know, both clinical value and economic value of all compounds.
What we're also doing with these late-stage compounds is really executing on the very robust life cycle programs for these compounds. As you also know, we filed a second-line gastric NDA in China for Fruquintinib, and we also have two additional registration studies ongoing in China, expect to file in the next year or two for these additional indications. This will hopefully guide us, you know, ex China development for these compounds as well. Same for Savolitinib. We have multiple programs. These two programs, salvo and also Fruquintinib, happen to be partnered up with AstraZeneca and also Takeda for Fruquintinib. We have to work with our partners very closely on this.
The second wave of compounds, our Seeking inhibitors, savolitinib, we expect to file later this year, towards the end of this year. We are awaiting the data to mature and to read out sometime in August, our first phase III registration study of Savolitinib in ITP. We also have a second registration study in anemia, which is progressing very nicely as well. This will be followed by our JAK delta inhibitor, which we believe is highly differentiated with a very favorable safety profile. We expect to file its first indication in China for third-line follicular and a second indication in second-line marginal zone lymphoma will follow sometime. Our EZH2 inhibitor, also in lymphoma, it's currently in a pivotal bridging study in China.
We expect to complete enrollment this year and file sometime next year. We have a lot going on. We have, you know, life cycles for our first wave and also initial NDAs for our second wave. Our third wave actually consists of four compounds covering both solid tumors and hematological malignancies progressing into registration studies. CRC will be positioned for future.
That's great. Maybe we can start with the commercial side of things and your domestic business in China. You were able to increase guidance already this year, which is, you know, relative to the street. Can you maybe provide a high level characterization of how the sort of post-COVID environment in China is from a commercial perspective? What are the trends or dynamics that you think investors may not be aware of there?
You know, we actually, during our annual results call, in March, I believe, end of March, we provided guidance for 2023. That's based on end of end of the year 2022 results and our expectations of our products' performance in China. Obviously, you all know that, first quarter, China was hit by a major outbreak of COVID, but now it's over. Now at the, you know, at the moment, the way things progressing, we are highly confident that we will be able to deliver the guidance this year. Basically, you know, China commercial continues to grow very robustly. This year in particular, Savolitinib was now included on the NRDL as well, although a bit late, it started March 1st.
Still, we are seeing a major effect on the product performance in China. We believe all three products will perform very well this year. Most importantly, I think with all these NDAs and NDA submissions we have lined up in the next maybe, you know, 6-18 months for all these compounds, plus our potential introduction of compound X China through potentially the end of this year. We expect our international income or revenues will kick in, you know, towards the end of the year and certainly into next year. We expect the China, you know, the commercial anyways, the revenues and profits will accelerate even at based on the rapid growth in China in the past few years.
Okay, great. Congratulations on the Fruquintinib, the NDA with priority review. With respect to the filing now that it's been accepted and you have priority review, what are sort of the intermediate steps that are left between now and your November PDUFA for you to, you know, complete the review process?
Yeah, very good question. Basically, priority review is a six-month time frame, and everything, all the activities are compressed into six months. We've been really working very closely with the review teams at the agency, and they have, you know, constant flow of questions, and we always respond as quickly as we can. In addition to the review related interactions, we have to also complete inspections, clinical inspections, as well as manufacturing sightings. These are expected to happen in the next couple of months.
Those are the sort of remaining items on, primary items on the checklist, clinical trial site inspections, plus.
Yeah.
Validation of commercial supply and so forth.
Right. Right.
Okay, great. With regard to the review, since you've been granted priority review, one of the interesting trends of the last year or so has been questions about foreign developed drugs and representation, I guess, for Fruquintinib. Would you expect an Adcom possibly to happen here given you are a foreign sponsor? How do you think about that, given that you have priority review?
Yeah. That's an interesting question, Paul, but I would actually characterize FRESCO-2 as a global trial rather than China trial. FRESCO is a China trial, but FRESCO-2 is actually a global trial with 150 sites across U.S, Europe, and Japan, Australia. It fully meet submission criteria for U.S FDA. Whether they, whether the agency requests an ODAC or a panel discussion, it's obviously up to the agency. We have not been notified to date.
Okay. You have not been notified at least of any current expectation for an Adcom at this point?
Right.
Okay, great. maybe turning to the commercial outlook for CRC here. you know, how would you characterize, you know, the current treatment practice and sort of the market options and market sizing currently? Then as you think about what you and your partner, you know, might do to help foster adoption of Fruquintinib down the road here in the U.S. market, you know, can you maybe characterize what some of your high-level plans are there?
Yeah. CRC is a major tumor type. It ranks in the top three across different regions in the world. Also the recent progress on IOs has not made a major impact on CRC. There's a clear, very strong unmet medical needs, particularly in the refractory setting. We are working very closely with our partner to, we've had a lot of interaction, a lot of meetings in terms of preparation for launch and strategic positioning for the product. We believe fruquintinib, you know, the data is demonstrated so far in various trials, clearly indicated it's a very active drug, even as a monotherapy. We believe it will provide a very much needed treatment option for these patients.
Ink, you know, at ASCO this year, we already presented multiple studies, most of them investigatory-initiated studies, looking at Fruquintinib, use of Fruquintinib in different settings in combination with IO. Work, you know, treating in combo or treating in sequence, a very interesting level of difference, perhaps because of the anti-angiogenesis activity by Fruquintinib, it primes the tumor vasculature, allowing better infiltration of cytotoxic T cells, for instance, enhancing clinical activity further. Also, multiple posters were presented at ASCO, looking at Fruquintinib activity in combination with Chemos in second line, even in first line with chemo and IO for. In CRC, we think Fruquintinib is proven very active and well tolerated
It can be combined with Chemo IO, and we believe it can be used in the future. Obviously, additional studies are required to confirm these activities. We believe it will play a major role, will have a major impact on CRC patients across the world.
That's really interesting. I know you said a lot of these studies were investigator sponsored, is there one or two that stands out in your mind, whether it's from a sequencing perspective or from a combination perspective, that looks most promising, that you would, you know, think about as a potential company-sponsored, study down the road, maybe in the frontline population, as you mentioned?
Yeah, I think, I mean, clearly, these data, while, you know, still emerging and early, you know, we believe, if confirmed, Fruquintinib in various settings, can provide, you know, additional clinical benefit to patients. In IO, well, we have sponsored a proof of concept study in combination with Sintilimab in China. We demonstrated basically PFS almost almost doubled, and OS significantly expanded. We are evaluating its potential to actually sponsor a potential registration study. However, multiple, not just one, multiple IITs or investigator initiated trials looking at usage of IO in sequence.
This is based on the hypothesis that at the refractory or late stage, these tumor vasculatures are very, very leaky now and preventing cytotoxic T cell infiltration effectively into the tumor. These investigators explored actually treating patients with Fruquintinib as a monotherapy in a third line. That's what it's approved for in China. At progress, when patients progress, they add IO on top of Fruquintinib, and these patients start to benefit again. This extends basically PFS much longer than when you add IO from the beginning, basically. Perhaps it is the effect of anti-angiogenesis from Fruquintinib. At the same time, it normalizes, to some extent, the tumor vasculature, allowing much better and more effective T cell infiltration.
Okay.
Into the tumor.
Very good.
Yeah. Speaking of your commercial partner, Takeda, you late last year announced a strategic shift or reprioritization, which ultimately led to this partnership as well. Can you maybe first remind us of the mechanics of your upfront arrangement with Takeda, how it's structured? You know, obviously, you're first focused on this Fruquintinib that's coming up here in November for the U.S.
Mm-hmm.
Could you maybe comment on how you think about future development with your partner in markets outside of the U.S. and outside of China?
We believe Takeda is the right partner for Fruquintinib. They are very strong. They have a very strong global presence commercially. Oncology is their priority. Fruquintinib will be a very important product for them. We are working very closely with them. You know, with regard to the payment, We already announced that we have received $400 million upfront. The remaining will be basically a milestone payment. Both regulatory milestones, but also commercial milestones in the future. That's how the deal is, was structured.
You know, in terms of future development, we are evaluating several indications of, you know, we already you know, alluded to a potential additional usage or different usage in CRC, whether it's IO combo or chemo combo into earlier lines, for instance. In addition to CRC, we believe the data generated in China so far, the studies we sponsored, clearly indicate potentials in gastric, non-small cell lung, and so forth.
Okay. Then in terms of your, you and your partner advancing in Europe and other geographies?
Obviously, you know, Takeda has the rights to Fruquintinib outside China. They will be leading all the studies globally, including U.S., Europe, and Japan, and other markets as well. All the future development will be led by Takeda.
Okay, great. Switching to other parts of the pipeline and maybe Savolitinib, can you maybe talk a little bit about the, where you are with the various development opportunities there, you know, maybe starting with Longan and your partner there? As a follow-up question in the EGFR space, how does the most recent updated Adura data make you think about the opportunity for Savolitinib and TAGRISSO in this EGFR MET population?
Yeah. Savolitinib, there are a lot of things going on, a lot going on with Savolitinib. In China, it was approved, well, for the exon 14 skipping non-small cell lung cancer. We are the sponsor in China, and we are conducting multiple registration studies, expanding its usage in different settings. We completed enrollment for the confirmatory study. In China, we expect to file maybe later this year or early next year. This will expand, you know, Fruquintinib into first line. A second study is in second line EGFR EGFR TKI refractory MET amplified non-small cell lung cancer. This study is enrolling.
We had some, you know, the COVID outbreak had some effect on the enrollment, but now we are working very hard to bring it back on track.
Mm-hmm.
We think we can file it probably towards the end of next year on it. We also have a study in first line called SANOVO. This is targeting patients with EGFR mutation, but also MET overexpression, so MET is activated in these patients. Adding Savolitinib upfront, hopefully can extend the progression-free survival for these patients. With regard to ADAURA, and there are other studies as well. We think it clearly demonstrated there is a strong on MET mechanism in second-line setting when patients progress on EGFR TKI. At the moment, double chemo is the standard of care.
In China, there is now PD-1 plus the EGFR plus double chemo, which is pretty heavy, and not a lot of patients can tolerate. ADAURA, basically TAGRISSO plus chemo, you know, maintaining EGFR inhibition, that's, you know, that is another incremental added benefit to these patients. All these are non-selected patient population, and, you know, I really hope that in the future, they can publish whether this treatment can benefit MET-amplified patient pop. What we think is that the study we are doing, specifically, adding a set MET inhibitor on top of MET-amplified patient population, we think this is a biomarker-selected patient population.
These patients will have confirmed activity with the combination. You know, they have all the data to rely on, basically. On top of that, all other treatment options, potentially, once approved, will be very complex with the chemo involved. Both, these will have, you know, chemo as the base, and just not very convenient in terms of compliance, but also patient tolerability with, you know, long-term chemo treatment.
Okay. Okay, great. Can you maybe speak specifically to the SAVANNAH trial and as well as your prior TATTON trial, how you think this is going to inform, you know, thinking about your potential re-registration path there, going forward for Savolitinib, particularly with regard to the U.S. and Ex-China markets?
Yeah.
As the next opportunity?
I think this is a very complex situation. Starting from the TATTON study and then followed by SAVANNAH study, we clearly demonstrated for these patients, about a third of patients progressed on EGFR TKI. These patients have MET amplification, and these studies demonstrated TAGRISSO in combination with Savolitinib provides very good clinical benefit to these patients. What we have done in the TATTON and in the early part of SAVANNAH, it's all about dose optimization. As you know, we compared the 600 milligram QD versus 300 milligram BID. We determined that 300 milligram BID is better to, you know, better tolerated, but also provides very good targeted coverage.
The other thing is biomarker selection, the cutoff. The SAVANNAH early part of the SAVANNAH is we also explored FISH IHC at different cutoffs. We determine IHC 90%, you know, for the for the three plus, and for the FISH gene copy numbers greater than 10. These are really important criteria for patient selection. Based on that, based on the data we have, we are aligned with the US FDA for the potential accelerated approval pathway. That's why late last year, maybe 3rd quarter last year, we converted SAVANNAH into a pivotal study for US. It's been, you know, it's been enrolling for the last nine months now.
We expect that this pivotal portion of the study will complete enrollment, fairly soon. After the PFS follow-up, we'll be able to file next year in the U.S. Globally, we are, in parallel now, conducting a phase III registration study. This study will serve as a confirmatory study to SAVANNAH in U.S., following potentially conditional.
This is your SAPPHIRE study.
That's the SAPPHIRE study.
Yeah.
Also will support global registration.
That's great.
Yeah.
This could potentially represent next year, your second, US, NDA filing or for your second drug.
Right.
Which would be potentially the fourth drug, China-developed drug to be approved in the U.S. after Savolitinib. That's great. Maybe turning to other aspects of the pipeline briefly for Surufatinib.
Mm-hmm. The opportunity in the Japan market. Can you maybe update us on your regulatory interactions there and, you know, talk about, you know, potential partnering in Ex-Asia markets for Surufatinib?
Yeah, happy to. Surufatinib, you know, obviously, we all know, US FDA recommended an MRCT in a representative patient population to support registration in the US. We are actually planning for that. Japan is, obviously, you know, Asian, comparing to China population, is very similar. We are in a pre-alignment with the PMDA, that a bridging study could potentially support registration in Japan, in- including the 2 phase 3 studies that we completed in China.
Mm-hmm.
That bridging study is data is maturing, and we expect to share the data with the agency, with PMDA, later this year. If the data supports and they still think the patient population, you know, as we discussed previously, the two China pivotal studies can support a registration in Japan, then we will prepare to file in Japan. Before that can happen, we expect to have a pre-NDA meeting, they call it pre-NDA consultation. That should happen likely later this year, likely fourth quarter.
Is the bridging study data something you would present at a medical meeting, possibly, or top line? How do you think about?
Oh, yeah, definitely.
Sharing that with the market?
Yeah, it definitely will be presented at a scientific conference.
Okay, great. Switching maybe to your hematology pipeline, you mentioned earlier an initial focus on follicular lymphoma.
Mm-hmm.
Marginal zone lymphoma there. Can you maybe talk about the developmental strategy there? I think people are probably more familiar with these diseases, primarily with the BTK space. Maybe you can talk about how you guys potentially fit into these indications and your commercial strategy going forward there.
I think our R&D strategy, both in solid tumors and in hem, is sort of about selecting targets ultimately will best cover the space. At the moment, we already have six compounds in clinic, and with, maybe potentially three more to come. I think now in the lymphoma we have our Syk inhibitor, PI3 Delta. We have EZH2. We actually have an internal program, EZH1 to do an inhibitor as well. All of these are targeted for, you know, various subtypes of lymphoma. And we also have a CD47 monoclonal antibody as well. We think the space, the targets we have relatively diverse and will cover lymphoma quite well.
In Leukemia, we have an IDH1,2 inhibitor, which covers one and two together, about 25%-30% of leukemia, AML, and also MDS. We have a second program, which at the moment is in this stage, and will be perhaps in clinic towards very end of this year. It's a Menin inhibitor, highly differentiated, very potent, very selective, and with very good safety profile. Menin covers about, again, one-third of AML. With also in the future potential to combine with CD47 as well. We think in leukemia, we are getting there now, with these targeted therapies. In multiple myeloma, we have also a couple of targets, including an ADC, which will be our first ADC.
Yeah.
In multiple myeloma.
I think people forget that you're expanding beyond small molecules.
That's right.
Right, into multiple modalities here. Yeah.
Yeah.
I talked about CD47, but also we're also working on Bispecifics. We're working on ADCs. Yeah, this will be a part of our pipeline.
Yep.
I'm going to make you answer a difficult question here is, if you have a early stage, you know, pipeline asset that you have to pick that you're most excited about, if you had to pick 1, what would you maybe comment on for the investors?
Yeah, I think it's hard to pick just a single compound. As I mentioned, we are more of a pipeline approach, trying to cover all the space. You know, going forward, I think in our investment in MAP kinase pathway, for instance, we have an ERK inhibitor in the clinic, which is doing quite well. We actually saw some data from RAS- targeted at ASCO, looking encouraging. I think our company is also, you know, demonstrating very good activity in phase I. We have a SHP2 inhibitor, which is going into clinic any moment, basically, looking for patients already. A very well-tolerated, highly potent SHP inhibitor. We also have two additional targets along the pathway, including RAS.
We all believe, RAS RAF pathway ultimately will require combinations upstream or downstream. Now we have SHP upstream, ERK1/2 the downstream, and also something in the middle, multiple targets. I think, we'll be emerging as a major partner in this pathway.
Okay, great. Thank you for that. I think, we're coming up on time here, so we'll end it on that note. My thanks to Weiguo and HUTCHMED.
Thank you.
For joining us today.
Yeah. Okay. Thank you very much.