HUTCHMED (China) - H2 2021
March 2, 2022
Transcript
Operator (participant)
Ladies and gentlemen, welcome to HUTCHMED Company Update. I will now hand the session to Mr. Christian Hogg, CEO of HUTCHMED, to begin today's presentation. Mr. Hogg, please.
Christian Hogg (Executive Director and CEO)
Thank you very much, Annika. Welcome everybody to the 2021 full year results and business update presentation today. Today we put out two announcements, the first being our 2021 full year results, which we want to spend the vast majority of our discussion today covering. The second was an announcement that's just gone out, detailing my retirement as CEO from HUTCHMED and the appointment of Dr. Weiguo Su as my successor and the next CEO of HUTCHMED.
I'd like to just spend a few moments talking about that and then put that aside and focus on our business. As many of you will know, I've been in China for the last 27 years, and I've been the CEO of HUTCHMED effectively for 22 years.
It's been a long journey, and it's been a great journey for us all, and the company from its sort of zero beginnings has come an awfully long way. I've obviously been accompanied on that journey by a fantastic management team and a group of people that are on the call today, which I'll cover in a moment. Recently in the last six months, my family have all effectively been moved back to the U.K. to schools. My three young sons all went to boarding schools in the U.K. My wife had to move to be close to them.
I found myself in Hong Kong all alone and with my young family as well as my parents getting older, my wife and I decided that it was time for us to move back to Europe. About five months ago, I informed the board and the nominations committee of this desire. We went through a very detailed and diligent succession process, which was already underway for some time anyway.
We concluded after looking at external and internal candidates and also asking the question, you know, could I remain CEO based out of Europe? We concluded that the best way forward for the business was to appoint Dr. Weiguo Su as the next CEO of HUTCHMED. I am fully supportive of this. I think it's a great thing for the business.
Weiguo, obviously many of you are aware of Weiguo and his, you know, his remarkable history and track record. It's a personal decision. It's a tough one for me because it's been a long journey that we've been on, but I have great confidence in the future of the company, the organization, the board and our shareholders.
You know, I just wanna say thank you to everybody for the support that's been given to me and the company through these years. I really look forward to seeing great things coming from Weiguo and the team. Leaving it at that, I would like to move now on to the corporate presentation. I'm sure we can answer any Q&A at the end.
Hopefully, I think we will all understand that the reasons for this move are purely based on my family responsibilities. On page three, you can see the agenda. I'll touch on some quick opening remarks, then we have Hong Chen, as is the convention in China, our Senior Vice President of Commercial in China, to talk about our commercial results in oncology. Then Weiguo and Marek Kania will talk about our discovery and development programs. Our CFO, Johnny Cheng, will talk about the financial status. Our Chief Operating Officer, Dr. Karen Atkin, will talk about operations and business development.
Finally, Weiguo will lay out the upcoming events and the final closing remarks, and then we'll go into Q&A. Next slide, please. HUTCHMED has built just a fantastic platform over the last 22 years. It gives me great pride to talk from this chart. You know, the organization now is over 4,600 personnel across the group. We have a team of 1,500 people in oncology and immunology.
We have a genuinely world-class global novel drug discovery and manufacturing operation in China. You can see that over those 20 years, led by Weiguo and the team, we have created 12 innovative small molecule drug candidates. We've built our team on the innovation side to over 800 integrated R&D staff.
There are few oncology and immunology teams of that scale anywhere, and, you know, gives us enormous capability. In the pink box, obviously led by Weiguo, but also by Marek in the rest of the world, the United States, Europe and Japan, we've built up great clinical development and regulatory operations. We're currently running over 45 clinical studies around the world.
Our first 3 novel drugs, our novel oncology drugs have all been approved and are now closer to approval outside of China. You know, creating the innovation in the blue box and bringing it to patients in the pink box. Now, on the right-hand side, you can see we've been investing greatly over the last 3 years in our commercial infrastructure led by Hong Chen. We now have a team, at the end of last year, with 630 people.
Actually, now it's closer to 750 people on the ground in China, covering all the main oncology hospitals in China. Hong Chen will take you through the results of last year and the very encouraging unaudited revenue results of the first two months of this year, which we've included in this presentation because of their importance.
We've also built under Marek and our commercial head in the U.S., Tom Held, a terrific group of people in the U.S. in commercial and medical affairs that now numbers over 50 people, all ready for the launch of our first product in 2022, surufatinib. Next slide, please. 2021 was an exceptional year. You know, it was extremely hard work by everybody on this call. We just achieved some fantastic things.
I put them into three buckets. On the commercial side, commercial results in China oncology, with the two launches, SULANDA and ORPATHYS, building the team up to 630 people, and then commercial results that Hong Chen will explain in a bit more detail later. Terrific progress commercially. The clinical portfolio really enjoyed step change progress. You know, we are running 13 registration studies and another 5+ are planned for this year.
ORPATHYS with AstraZeneca has stepped up to being a truly global initiative. We've just received word from Astra that we've triggered our global phase III milestone, $50 million milestone in the last couple of days. That means that we are now moving very rapidly into a global phase III for the savolitinib combo.
Major data presentations, a number of new assets have been put into the clinic and a good deal with Epizyme on TAZVERIK. A lot of progress on the portfolio. The last box is the global ambition. I mean, one of the things that differentiates HUTCHMED from many China biotechs is that we don't see ourselves as a China biotech.
We see ourselves as a biotech company that's bringing homegrown Chinese innovation to the global market. That development organization, clinical regulatory team in New Jersey and in Europe of now 130 or so people, is allowing us to do that. We've got seven assets in clinical trials outside of China.
Fruquintinib's just completed its global phase III, the FRESCO study, so we're getting hopefully a readout of that middle of this year, which will be an enormous step for fruquintinib. Surufatinib, the U.S. NDA and European MAA are filed and under review and in the very late stages of those processes.
We're getting ready for the launch, the second half of the year on surufatinib. You know, 2021 has just been a great year for us all and we've positioned ourselves very well for 2022. Next slide, please. I'll stop there and hand it over to Chen Hong to talk about the progress in commercial so far this year and last year. Over to you, Chen Hong.
Hong Chen ) (SVP)
Thank you, Christian. Next slide, please. HUTCHMED started the on-the-ground promotion activities for ELUNATE in Q4 2020. 2021 was the first full year for HUTCHMED to commercialize its innovative products, both ELUNATE and SULANDA, through its own commercialization platform. The first slide shows HUTCHMED commercialization capabilities in terms of team size, hospital pharmacy listing, hospital and city coverage.
We can see that the team size increased to 630 by the end of 2021 and will continue to expand along with the business growth. The growth for hospital pharmacy listing, hospital and the city coverage were 131%, 73%, and 42% respectively, comparing with the end of September 2020. Next slide, please. This slide shows the market performance of ELUNATE.
ELUNATE achieved $71 million in market sales in 2021, with 111% growth versus 2020. More than 22,000 first-line CRC new patients were treated with ELUNATE in 2021. Around 4,800 educational events were executed in 2021 for ELUNATE. According to the post-launch checking study implemented by IQVIA, ELUNATE achieved the share leadership by exceeding Cyramza , which was launched two years earlier, with ELUNATE capturing 39% of patient share in Q4 last year.
It has successfully passed the NRDL review last year with only 5% price cut versus the 2021 NRDL price. From the January treated patient completion and the unaudited first two months sales of 2022, we can see ELUNATE continues to keep very fast growth. Next slide, please. This slide shows the market performance of SULANDA.
SULANDA was launched in January 2021 and achieved $11.6 million in market sales for the first year. About 4,800 patients were treated by SULANDA, and more than 12,000 HCPs were involved in SULANDA academic events in 2021. Comparing with the average 64% price cut across all oncology NRDL products, we were successful with SULANDA entering to the NRDL with a 52% price cut.
We can see the treated patient number in January this year, which was SULANDA's first month for reimbursement, was sevenfold that seen a year ago. The value growth increased up to 21% in January, February this year, although there was the price cut impact. Next slide, please. The last but not least slide shows the performance of ORPATHYS.
ORPATHYS is the first-in-class MET inhibitor and was launched in July 2021 by our commercial partner, AstraZeneca, in China. Around 1,900 new patients were treated in the second half of last year with about $60 million. There are about 13,000 new patients per year with MET exon 14 skipping for non-small cell lung cancer. Even more importantly, there are over 100,000 MET-driven patients in China across all indications.
Seven registration studies are already ongoing in China to address these patients in lung, kidney, and gastric cancers. AstraZeneca is a strong commercial partner. It has well-established and extensive commercial platform on lung cancer business. There are a lot of synergies between ORPATHYS and AstraZeneca's other lung cancer products.
We can see ORPATHYS also had a good start in the first two months of this year with $7.4 million in market sales. Overall, we have had a very good year in 2021 and are off to a strong start in 2022. We expect this momentum to continue to go from strength to strength as our commercial team continues to build over the balance of 2022. Thank you.
Christian Hogg (Executive Director and CEO)
Thanks, Johnny Cheng. Now we'll hand it over to Weiguo Su and Marek Kania to take us through the discovery and development programs. Weiguo Su, Marek Kania? You may be on mute.
Weiguo Su (CEO and Chief Scientific Officer)
Sure. I was, but okay. Good evening, good morning. Marek and I will give you an update on the pipeline. Next slide, please. 2021 was a busy year, a year with significant progress on our pipeline, highlighted by NDA approvals for savolitinib and surufatinib in China, NDA MAA submissions for surufatinib in the U.S. and EU. At the same time progressing our second wave of compounds, amdizalisib and sovleplenib, into registration studies in China.
Next slide. Well, behind the initial approval of savolitinib in China, together with our partner AstraZeneca, we are now shaping a very strong life cycle management strategy with seven studies with a registration potential across lung, kidney, and gastric cancers. Next.
Three of these studies are in EGFR mutant non-small cell lung cancer with MET amplification or overexpression using Tagrisso/savo combo, supported by POC data from TATTON, ORCHARD, and the ongoing SAVANNAH studies. Next slide. The SAMETA study is a global phase III in MET-driven PRCC, supported by strong data from the CALYPSO study in combination with Imfinzi.
To date, PRCC patients have a poor prognosis and very limited treatment options. Moving to surufatinib, let me first ask my colleague, Dr. Marek Kania, Head of HUTCHMED International, to give you an update on the global activities.
Marek Kania ) (Executive VP, Managing Director and Chief Medical Officer, International)
Yes. Hi, everyone, Marek. On the surufatinib arm, we spent the majority of last year progressing our regulatory process in addition to conducting our combination studies with a number of combination partners, including PD-1 with BeiGene. As you can see on the slide summarizing our package for regulatory submissions across the U.S., EMA, and in the near future, PMDA in Japan, we progress this package through a regulatory process. Just as a reminder, this package consists of two positive phase III studies conducted in China supported by a robust package of U.S. patients from U.S. studies.
As Christian alluded at the beginning, we are in the late phase review process in the U.S., pending some remaining inspections in the clinical site as well as a mandatory inspection on the manufacturing site. On EMA side, we passed 120-day assessment moving to late phase review process. Next slide, please.
While we are progressing our review process, we also, as Christian said, aggressively preparing for a potential launch, building a very capable medical affairs team as well as very strong commercial team, currently 54 FTEs, and at launch will be 84, strong effort led by Tom Held. Next slide, please. Mike, over to you.
Weiguo Su (CEO and Chief Scientific Officer)
Lifecycle management program for surufatinib is currently focused on PD-1 combinations. These are toripalimab in China and tislelizumab globally. Based on the encouraging POC phase II data, we initiated phase III, the SURTORI-01 study in second-line neuroendocrine carcinoma, and we are preparing to initiate another phase III in second-line esophageal cancer later this year. Other indications will be considered if more mature data will support. Now moving to fruquintinib. Next slide. Back to Marek.
Marek Kania ) (Executive VP, Managing Director and Chief Medical Officer, International)
Yeah. Let me quickly summarize a huge effort in 2021, progressing our fruquintinib program, which, in addition to conducting our combination studies with also PD-1 combinations, our majority of effort was focusing on successful execution of FRESCO-2, a global study. As a reminder, this is truly first phase III global study conducted in 14 countries across 116 sites. I'm pleased to share that as of December, we reached full enrollment, and it just happened in 15 months.
Despite of pandemic limitations, it was huge effort on teams, and we are grateful for physicians and patients willing to join this study, which really highlights high unmet medical need, which was assumed before starting this study that also confirmed and gave us high confidence.
This study will complement our robust international package, which will be based on our upcoming NDA, MAA, and PMDA submissions. Just important statement to make, this package was fully aligned with U.S. FDA and EMA through scientific consultation as well participation of Japan will assure us our good start with PMDA submissions. Next slide, please.
Weiguo Su (CEO and Chief Scientific Officer)
In China, we continue to expand lifecycle management programs for fruquintinib. The FRUTIGA study in second-line gastric cancer in combination with paclitaxel is expected to complete enrollment in second half of 2022, and top line results mid next year. Combination with the PD-1 inhibitor sintilimab, currently second line endometrial cancer is already in registration study with HCC and RCC registration studies to follow during 2022.
Moving on to our second wave compounds, amdizalisib, the PI3Kδ inhibitor, and sovleplenib, the SYK inhibitor, both with applications for hematologic malignancies. Next. Speaking of the hematologic malignancies, we are building a very strong portfolio. To date, 6 compounds are already in clinics with several more in discovery. Together, the portfolio provides a broad coverage of 3 subtypes, lymphoma, leukemia, and multiple myeloma, with a diverse types of MOAs, a strong potential for combinations.
The two lead compounds, amdizalisib and sovleplenib, progressing to registration studies in China and making good progress as well in global studies. Next slide. The China multi-cohort phase Ib study continues to enroll in MCL, CLL, and PTCL. Follicular and marginal zone have moved into phase II registration studies last year based on the favorable efficacy and safety profile data in follicular published at ESMO 2021.
China CDE granted amdizalisib a breakthrough therapy designation for follicular. We expect to complete enrollment for both indications this year and potential NDA submissions during 2023. Additional indications will be considered for registration studies if data support. Several exploratory studies, including combination with tazemetostat, are preparing to start this year. Next slide. Back to Marek.
Marek Kania ) (Executive VP, Managing Director and Chief Medical Officer, International)
Yeah. On the global side, we are conducting parallel developments for amdizalisib, and based on our initial promising results in the early phase of our development, we expanded significantly our ongoing study into more than 200 patients, and added several cohorts, as you can see.
We believe in the second half of the year we'll be in a very good position to not only having a more robust data set, but also longer follow-ups, which will inform our next phase of development decisions. At the same time, we're also embarking on combination studies, as we speak with several potential combination partners. Next slide, please.
Weiguo Su (CEO and Chief Scientific Officer)
Continue on to our SYK inhibitor, sovleplenib or HMPL-523. In addition to lymphoma, we completed a phase I/II study in ITP last year. SYK is a validated target for ITP. As you know, fostamatinib was approved in 2018. Sovleplenib is a much more selective SYK inhibitor and demonstrated favorable safety profile with much improved GI and hypotension safety profile.
The level of efficacy seen in this phase I/II study was also very promising. OR 80% and durable OR 40%, albeit with small sample sizes. Based on the favorable efficacy and safety, CDE granted sovleplenib breakthrough therapy designation for ITP. The phase III study is now ongoing. We expect to complete enrollment by end of 2022 and top line results in 2023. Next slide.
Marek Kania ) (Executive VP, Managing Director and Chief Medical Officer, International)
On a global side for sovleplenib, as you can see, we are conducting a really parallel development as well, and this expansion cohort study in lymphoma is conducting as we speak. We hope to report more data by end of the year, which will inform our next phase development in lymphoma. At the same time, we are preparing IND for our non-malignant indication in ITP, again, as Weiguo mentioned, based on promising signals from our China studies. Again, this part will be parallel development. Next slide, please.
Weiguo Su (CEO and Chief Scientific Officer)
Okay, just a quick update on tazemetostat. Tazemetostat is a first-in-class EZH2 inhibitor approved in the U.S. We believe EZH2 is an important target with potential for both solid and blood tumors. Last year, we entered into a collaboration with Epizyme and gained rights for Greater China. Obviously, our top priority is to bring it to registration in China quickly. Currently, the bridging study IND in follicular has been cleared, and the study is ready to go.
A second registration study, the global SYMPHONY-1 in second-line follicular will be starting off shortly as well. In addition, we are interested in exploring a broad range of indications, including in combinations with amdizalisib, fruquintinib, and surufatinib. Globally, we are also in discussion with Epizyme to potentially explore combination with amdizalisib in lymphoma. Next slide.
To sum it up, we are expanding our registration studies with our late-stage compounds both in China and globally. We anticipate this to continue with more compounds reaching registration and approvals. Next slide. At the same time, our portfolio continued to grow. Four new compounds entered the clinics recently. Our goal is to build a pipeline that can provide a good coverage of various tumor types with diverse MOAs that allows science-based combinations of our products to further improve efficacy and maximize the value of our products. Next.
Christian Hogg (Executive Director and CEO)
Great. Thank you. Thank you, Weiguo. Thank you, Marek. Now we'll hand it over to Johnny Cheng, our CFO, to cover on a high level the financial results that were published today. Johnny?
Johnny Cheng (CFO)
Thank you, Christian. Next slide. We have a strong balance sheet end of last year with cash resources over $1 billion, contributed by cash proceeds from various sources. The IPO, the PIPE, and the divestment of our non-core OTC business. Moving on to our operating results in the next slide. Group revenues up more than 50% to over $350 million.
The oncology revenue was in line with our guidance, approximately 4 times of 2020 revenues. Our R&D investment up over 70% to around $300 million. Investment in U.S. and EU have increased significantly and is now at a scale similar to China. The divestment of the OTC business, together with the income from the other ventures, have helped to offset the cost of the R&D investment.
As a result, the overall net loss of the group was $195 million. Next slide, please. On this slide, we can see there are still a lot of value within our other ventures. Looking at a high level, those businesses have delivered over half a billion of net income in the last 20 years. If we divest further the non-core business, it can help to fund our R&D investment in oncology. Moving on to the next slide. Well, you all heard from Hong Chen talk about the commercial progress that's been made and the momentum that continues into this year.
We also see strong initial results in January and February. As a result, our guidance for 2022 is $160 million-$190 million revenues from the oncology business. This is China only, so we will incorporate the global revenues in due course when we see the approval coming outside of China. I will now pass to Karen.
Karen Atkin ) (Executive VP and COO)
Thank you, Johnny. Next slide, please. We're building a world-class leadership team at HUTCHMED, in line with our ambition to be global, innovative oncology biopharma company operating to international standards. What's really notable about our team of leaders is their long tenure and their track record at HUTCHMED, but also in other major multinational pharmaceutical companies. Tom Held, our U.S. commercial head, and Selina Jiang, who joined us recently as our new head of global HR, and myself as the Chief Operating Officer, have all joined more recently to fill in new roles in the company.
Actually there are many more highly experienced leaders who have joined us beyond the few that you can see in this white box on the slide. Next slide, please. We've doubled the number of people in the oncology team in the last two years, and we've got plans to grow further.
We currently have 1,500 people, and last year we added more, particularly in clinical and regulatory, so that we can run our China clinical trial programs with an in-house team for better speed and quality. As well as building out our international clinical and regulatory team to ensure we can run truly global development programs. As you heard before, we've been expanding our oncology commercial team, and at the end of last year, we had 25 people in U.S. commercial.
It's now expanded to over 50 people in U.S. medical and commercial in anticipation of the launch of savolitinib this year. Next slide, please. We've had clear success with our in-house R&D pipeline, as evidenced by the three innovative medicine approvals in China. Scientific partnerships are also very important to us. From a business development perspective, we're engaged in four key activities.
Firstly, we have long-term strategic partnerships with multinational pharmaceutical companies such as AstraZeneca and Eli Lilly. Secondly, pipeline synergy collaborations, as we really seek out the best novel combinations, for example, with Epizyme, Junshi Biosciences, Innovent and BeiGene. We are also looking to partnerships to increase our bandwidth and finally, to gain new capabilities in oncology, for example, in the biologics area, potentially through strategic acquisitions. Next slide, please. We have a clear strategy from a geographical perspective.
In the largest two markets, the U.S. and China, we will launch with our in-house team while partnering out elsewhere. We have the cash and the resources to be able to commercialize ourselves in China and the U.S., which makes sense as we can retain the maximum economic value from our innovations.
We already have a strong commercial track record in China, and our U.S. team is moving forward now with 7 clinical stage assets, while also setting up our savolitinib launch team. For the 3 late stage products in the international team, we have clear registration plans in place for the U.S., EU and Japan, with clinical studies underway, and we have the capability to self-develop in those regions.
However, for commercialization in Europe, Japan and the rest of the world, we recognize the complexity with more than 100 different countries, each requiring in-depth local knowledge to be successful. We've chosen to look for strategic commercial partners outside the U.S. and China, starting with savolitinib and fruquintinib this year. I'd now like to hand over to Weiguo.
Weiguo Su (CEO and Chief Scientific Officer)
Thank you, Karen. Next slide. A quick update on the upcoming events. In China, we expect 2022, a year of work with so many studies ongoing, and 2023, a year of results and potential regulatory submissions. Obviously, we will be publishing scientific data along the year. Next slide. Globally, 2022 will be a transformative year with important milestones to hit, including potential savolitinib approval and launch and fruquintinib with a FRESCO-2 to read out and potentially file.
Next slide. To conclude, we expect the momentum to continue in 2022. China commercial will continue to grow and the U.S. set to start. Development programs continue to expand with potentially multiple NDAs lined up for the coming years. Our organization is set to grow to support the execution of our goals in the next few years.
2021 was a busy and fulfilling year, and we expect 2022 to be equally busy and exciting. Next slide. Thank you. I think we are ready now to take questions.
Operator (participant)
Thank you. We will now begin the question and answer session. All you participants with questions to pose, please press zero one on your telephone keypad and you will be placed in the queue. To cancel the queue, please press zero two. Once again, zero one on your telephone keypad now. Our first question comes from the line of Alec Stranahan from Bank of America. Please go ahead.
Alec Stranahan (Vice President, Senior Equity Research Analyst)
Hey everyone. Thanks for taking our questions. Christian, wanted to offer our congratulations on your move. Obviously quite a legacy you leave behind at HUTCHMED. I guess two questions from us. First, could you maybe talk about choosing toripalimab for the SATORI-02 study versus some of the other PD-1 such as atezolizumab? Is there anything emerging from the clinical data that would suggest these assets synergize differently with surufatinib or any of your other assets?
As a follow-up to that, when you think about the combination strategies going forward, how much of your approach will be on top of the approved therapies like PD-1s versus rational combinations in-house together with some of your earlier stage assets? Secondly, could you talk a bit about what led to declining the NRDL inclusion for SAVO?
I'm guessing this was about the balance of access, price, and concessions, but any color on your thoughts or AstraZeneca's would be great. Thanks.
Weiguo Su (CEO and Chief Scientific Officer)
Um.
Marek Kania ) (Executive VP, Managing Director and Chief Medical Officer, International)
Maybe Weiguo. I think during the Q&A, Weiguo will lead it. Thank you, Alex, for your kind words, and maybe Weiguo handles the PD-1 questions, and I can maybe give a couple of comments on savolitinib NRDL.
Weiguo Su (CEO and Chief Scientific Officer)
Yeah, sure. Thanks for the question, Alec. SATORI-02 is the registration study in esophageal cancer being planned, and we anticipate the start sometime this year. Now, the combination with tislelizumab is actually in exploratory stage. Maybe Marek can give you some more details.
Marek Kania ) (Executive VP, Managing Director and Chief Medical Officer, International)
Yeah, Alec, thanks for the question. You know, we didn't go into details, but both across fruquintinib and savolitinib we have multi-cohort combination studies going on with tislelizumab. We hope by the end of the year we'll be in position of formulating some good proof-of-concept data across several cohorts. You know, we have colorectal, we have small cell NET and so on. We'll be definitely focusing very eagerly on signals from those studies. That's a good question from U.S. perspective, obviously that's our first priority.
Weiguo Su (CEO and Chief Scientific Officer)
Thanks, Marek. With regard to your second question on our kind of preference for combinations, you know, approved versus our own novel drugs, the PD ones are really a window of opportunity that we pursued and really generated very promising data that now resulted in multiple registration studies. Going forward, obviously, we would love to combine with our own products in our pipeline and really to address strong unmet medical needs.
Obviously all these combos will be science-based. As I was walking through the pipeline chart, our goal is really to design and build a pipeline with diverse MOA that can cover the tumor types and that offers highest potential for science-based combinations.
I think going forward you will see a lot more such combinations. Maybe Christian can touch on NRDL for SAVO.
Christian Hogg (Executive Director and CEO)
Thanks. Thanks, Weiguo. Yeah, it was a tough decision. AstraZeneca and HUTCHMED agreed our strategy going into the negotiations for SAVO. The gap was just too wide. The regulatory authorities wanted a deeper discount than we were willing to accept. One of the reasons that we didn't accept it is because savolitinib is a first-in-class asset in China.
We're the only selective NET inhibitor in China. So until such time as that changes, I think we're happy to go out and self-pay with big patient access programs to help those lower income patients access the drug. My sense is that the from a competition standpoint, unlikely to be anything coming to market anytime soon.
I imagine we'll go back to the discussions with the regulatory authorities for the NRDL discussion this year. We'll go into it with an open mind, but it will be dependent on the competitive environment, and a reasonable discount versus an excessive discount.
Alec Stranahan (Vice President, Senior Equity Research Analyst)
Got it. Makes sense. Thank you.
Operator (participant)
The next question comes from the line of Rajan Sharma from Deutsche Bank. Please go ahead.
Rajan Sharma (Equity Research Analyst)
Hi, thanks for the questions. Christian, congratulations on your time at HUTCHMED and best of luck for the future. My first question actually relates to the obvious change in CEO and just, you know, you mentioned that it was something that you'd informed the board about five months ago. So just wondering why there's the kind of immediate change in CEO as of tomorrow and why there's no kind of longer transition period. Maybe I'll follow up with a second one afterwards.
Christian Hogg (Executive Director and CEO)
Yeah, thanks Rajan. I'll answer that Weiguo. I mean, you know, none of these things happen overnight. You know, I've been away from my home for 34 years. You know, as I said, I've spent 27 years in China. I'm not sure there are too many Western executives that have spent 27 years in China.
As my family and my children have been growing up, I, you know, it's been in the back of my mind. But I have to say, the move of my entire family to the U.K. just for their education, that really was the event that sort of pushed me to the point of realizing, staying in Hong Kong and Shanghai for myself was not sustainable. Yeah, we approached the nominations committee and the board in September, or I did. We have an ongoing process that we just sort of escalated the intensity of that process. It does seem, I'm sure, to everybody that hears this news today as quite a surprise.
Obviously it's a sensitive matter that we couldn't signal to the market until we were ready. You know, as we worked through as a board and concluded that Weiguo Su was head and shoulders the best candidate for the succession, we've now come with this as quickly as we could. The reason for no extended transition is we feel that personally, you don't wanna have the old CEO hanging around. It's even hard enough in an analyst call today, right? You certainly don't want it in the long term. Weiguo Su has been deeply involved in all aspects of the business over the last 16 years.
There's no need for a transition, as it were, other than in my role as a strategic advisor, to be there for Weiguo Su to help him in any way I can, with the areas that I've been managing independently over the last few years, and also to help the board and Simon To and the Hutchison group, you know, to keep the momentum going. I'll be there as a strategic advisor, and as a result, there's no need for some sort of extended transition. Hopefully, that answers your question.
Rajan Sharma (Equity Research Analyst)
Yeah, that's helpful. Thank you. Then just maybe one on operations and on a Hutchison side of things. Just, you know, you've flagged in the release that you would look at obviously non-core asset divestments as a potential for future financing, but then also potentially a second or fourth listing in Shanghai. Could you just perhaps talk about your preference for either of those? And if you do choose to go for a Shanghai listing, would that mean that you would delist from another exchange?
Christian Hogg (Executive Director and CEO)
Maybe I'll ask.
Um, I'll ask Simon To to answer that question, maybe Johnny to supplement. Weiguo Su, if that makes sense to you.
Johnny Cheng (CFO)
Yep. Absolutely. I was going to say yes. Yep.
Simon To ) (Chairman and Executive Director)
Okay. Thank you. This is Simon To here. Yes, as you know, we divested of the Guangzhou Baiyunshan Pharmaceutical, you know, company, and it was a very good, you know, return for our investment in that company. We of course have this other TPN business in Shanghai, you know, the one that is called, we call SHPL, but you know, it sells the She Xiang Bao Xin Wan, you know, which is a cardiovascular prescription medicine.
This is a very successful company. A lot of people wanting to buy this asset. We of course, you know, if we feel that we get an offer that is extremely attractive, we'll consider it. That would be very good for the existing shareholders of HUTCHMED. You know, if we can raise a bunch of money, you know, it's non-dilutive financing.
That would, you know, make us very, you know, cash rich. You know, we have $1 billion in the bank now. You know, if we could build that up, and that will give us plenty of runway in order for us to apply for a listing in Shanghai, you know. Yeah, that's what we are considering right now.
Christian Hogg (Executive Director and CEO)
Thanks, Simon. Johnny
Simon To ) (Chairman and Executive Director)
Thank you.
Christian Hogg (Executive Director and CEO)
Any additional comments?
Johnny Cheng (CFO)
No. I think we will continue to discuss explore with interested parties. As our chairman, Mr. To said that this SHPL is a very attractive business. There are many parties who are interested, and we will be very selective.
As far as the listing in Shanghai, I think we understand the process have been extended previously, but now it seems that the authorities in China have been able to speed up the reviewing process. We will again go back and reveal the plan, and then if the timing is right, we will initiate some of this initiative that we have looked into earlier. Yeah.
Rajan Sharma (Equity Research Analyst)
Okay. Thank you very much.
Operator (participant)
The next question comes from the line of Louise Chen from Canaccord Genuity. Please go ahead.
Louise Chen (Managing Director & Senior Equity Research Analyst)
Thank you for taking my questions. Christian, thank you for all your contributions to HUTCHMED, and good luck with all your future endeavors. My questions are as follows: Can you help us think about the global sales potential of your oncology and immunology portfolio, and how you plan to get there? On the cash balance, you have a very strong cash balance. What are your capital allocation priorities? Last question I have is, how should we think about the trajectory of the U.S. launch of savolitinib? What kind of sales should we expect to see this year, and what is the U.S. sales potential of this drug? Thank you.
Weiguo Su (CEO and Chief Scientific Officer)
Okay. On the global sales, I'll ask Marek and Christian perhaps to take the question.
Marek Kania ) (Executive VP, Managing Director and Chief Medical Officer, International)
Yeah. Thank you, Weiguo. Louise, obviously, this year's sales potential, we're not going to speculate on numbers. Everything depends on the timing of approval, and as you observe, dynamics with pandemic-related scheduling and PDUFA changes, you know, we are not going to speculate when it will happen. We're still pending some inspections.
That all depends. Team will be ready to maximize our launch readiness and commercial activities post-launch. We are confident that with our profile, you know, this will be a good place in the setting. You can obviously do your modeling in appropriate ways, but we feel very confident.
Overall, your second or your first part of broader portfolio performance, as you've seen, we're putting really robust efforts in the global development to maximize our global future commercial potential. Obviously, starting from patient in mind, robust clinical trials and bringing those patients representing multinational, you know, realities of clinical practice. You know, with fruquintinib, we believe this differentiating profile has you know plenty of space to grow in third-line class colorectal setting.
We feel very confident even now on the pending top-line results of FRESCO-2. Again, this space is highly underutilized from approved agents perspective. Only 25% of agents approved in this setting is being used. Everything else is different things. Fruquintinib will have plenty of space to grow there.
On the broader portfolio, obviously, we're led by science and to maximize our positioning in the respective settings, focusing really on bringing clinical benefits. We believe that will lead to the results of commercial success as well. I will stop here, and Christian maybe if you want to add something.
Christian Hogg (Executive Director and CEO)
Yeah. Louise, it's thanks, Marek. It's a good question. I think, you know, we provide in the appendices to our corporate presentation quite detailed analysis of the global patient populations and the indications we're going after for fruquintinib and surufatinib. I think if you're modeling it, you can just assume the levels of pricing that you would expect for these targeted selective targeted therapies in oncology.
Yeah, obviously fruquintinib and surufatinib have many hundreds of millions of dollars of global potential outside of China and inside of China as well. So we'd obviously hope that both of these drugs become billion-dollar drugs. That's what our hope is. On the capital allocation, you know, you can see it.
Johnny shared with you the financial results from this year, where the investment in R&D around our international activities has now effectively caught up with our investment in China in our clinical regulatory operations, so about $150 million each of R&D spend. I would expect as the pipeline continues to develop, we'll see those continue to increase in both areas, but probably particularly outside of China.
That's how we think about. But as Marek says, we allocate capital based on the science, based on the clinical data. As we see exciting clinical data come forward, I'm sure we'll be allocating aggressively. Weiguo, any thoughts or comments on that?
Weiguo Su (CEO and Chief Scientific Officer)
I think in general, you know, obviously, supporting R&D activities and expanding our manufacturing capacity and ultimately and also building our organization further to support our goals, you know, particularly on the globalization side. I think you know these would be certainly our top priorities. Moving to the third question with regard to the trajectory of the U.S. launch of savolitinib, I think Marek can probably shed some light on that.
Marek Kania ) (Executive VP, Managing Director and Chief Medical Officer, International)
Well, Weiguo, I can kind of address that. You know, obviously, depending on the timing of approval and obviously our strong positioning, obviously a few factors depend on the final label and the timing of start of launch. You know, rest assured we'll be very aggressively positioned to maximize our first six months of launch trajectory, which is usually predictive of your overall success. Again, similar to colorectal, only less than 10% of patients are treated currently with targeted agents. Again, surufatinib profile has plenty of space to play.
Louise Chen (Managing Director & Senior Equity Research Analyst)
Thank you.
Weiguo Su (CEO and Chief Scientific Officer)
Good.
Operator (participant)
The next question comes from the line of Yang Huang from Credit Suisse. Please go ahead.
Yang Huang (Director and Senior Analyst)
Thank you. First of all, I'd like to, I'm sorry to see you leave, Christian. You have been doing great work for the company. Also to Weiguo, congratulations to be going to become the CEO of the company. Wish you the best. My question will be centered around fruquintinib, the FDA review process. In your presentation, you mentioned the mid-cycle review meeting have been completed. Do we have any kind of any color on the meeting? Also, manufacturing and the clinical site inspection is still pending. I assume there's going to be virtual inspection.
Will there be any issue given recent days, I have seen some Chinese company, when they did some virtual inspection, it seemed to be some problem, and they just want to get a color on the inspection side. Then lastly, for the fruquintinib, if we got approved in the U.S., what could be the label? Will it say second line, third line, or how exactly we expect the label to be? Thanks.
Marek Kania ) (Executive VP, Managing Director and Chief Medical Officer, International)
Yeah, thank you. Marek, do you want me to address it?
Christian Hogg (Executive Director and CEO)
Yes. Marek, go ahead.
Marek Kania ) (Executive VP, Managing Director and Chief Medical Officer, International)
Thank you for your question. You know, regarding your question number one, our ongoing review, obviously I'm not going to speculate about outcomes nor sharing details of the review, but, as you know well, regulatory review process is long, complex and robust. You know, sponsor has a role to play and the regulatory agencies has very important role to play.
This process needs to go through full completion. There are multiple steps of engaging very collaboratively with the agency, answering many, many questions. You know, that's what I can say. You know, there's still definitely a few months to go through. Regarding your question about inspections, from FDA perspective, FDA does not like virtual inspections. I think that's the reality of today.
Which, as you've seen across a number of sponsors and indications and applications, the FDA is in a backlog of inspection issues, including and not just China-related, but also domestic in the U.S. due to COVID limitations. You've seen trends that the FDA stopped even rejecting or doing that. They just go through their workload. We do expect that whenever possible, those physical inspections will have to happen.
Obviously, we hope that the regulations, the limitations in China to travel and move, will be somewhat, you know, limited and allow those inspections to happen. A manufacturing inspection is a mandatory process for the FDA to complete. Obviously, we're ready on both fronts whenever the FDA issues our notifications.
Your last question about labeling, you know, the NET space is not really line specific. You know, we indicated in a prior information we are our label is in advance NET, both NET and epNET and pNET indications. That's our ongoing review labeling. We will be receiving label and we'll be in that labeling discussions, it's still pending, so we're not there yet. That was our strategic aim, and we continue to do that based on both a standard pNET and a standard epNET study. I hope it answers your questions.
Christian Hogg (Executive Director and CEO)
Thanks, Marek.
Yang Huang (Director and Senior Analyst)
If I may, a quick follow-up. Also in your presentation, we showed, when looking at the prior therapy, right, the China phase III data still shows some difference with U.S. bridging study, right? For example, if we look at prior everolimus, the use in China, the percentage is very low, and in U.S. bridging study it's very high, close to 100%. Will that indicate there's some kind of standard of care difference between U.S. and China?
Marek Kania ) (Executive VP, Managing Director and Chief Medical Officer, International)
Well, as we said, standard of care is broadly similar. Obviously, there are some differences. The timing of approvals in China at the time of the conduct of the SANET studies, you know, there will be limited access to targeted agents at some point and the timings of approval. You know, when you look at the historical data of SANET studies, you will see some differences.
Keep in mind, the bridging study across both pNET and epNET in U.S. was conducted in a highly refractory population, you know, lines of prior therapy of up to eight lines. You know, you will see obviously that population. There was no point of creating full parallel, but really demonstrating safety and efficacy data as well as being source for PK analysis which, you know, consistent results.
Yeah, you cannot compare one to one, you know, between a phase III study conducted historically before and a highly refractory population in the U.S., one phase I study.
Yang Huang (Director and Senior Analyst)
Okay.
Marek Kania ) (Executive VP, Managing Director and Chief Medical Officer, International)
Even, you know, with the refractory results you see, you know, quite impressive clinical benefit in this highly pretreated population. That's what encourages us. That's what drove us to submission, actually, in U.S. and Europe.
Yang Huang (Director and Senior Analyst)
Thanks.
Marek Kania ) (Executive VP, Managing Director and Chief Medical Officer, International)
You're welcome.
Operator (participant)
The next question comes from the line of Kelly Shi from Jefferies. Please go ahead.
Kelly Shi (Managing Director & Senior Equity Research Analyst)
Hi, This is Ziyi Chen at Jefferies. I'm dialing on behalf of Kelly Shi. Congratulations on the great year. I just have two quick questions. Number one, I think in January, fruquintinib showed great data in its phase I metastatic colorectal cancer trial. Just wanna understand whether the trial data will have any impact on the timeline of your FRESCO-2 trial and also the maybe subsequent potential filing for NDA.
My second question is your commercial buildup in the U.S. I understand your China commercial team has progressed very rapidly. Looking at the U.S. personnel on slide 37, you showed the 25 people in the commercial team in the U.S.
Could you share your plan for your U.S. commercial buildup, maybe this year and next year? Thank you.
Weiguo Su (CEO and Chief Scientific Officer)
Yeah, Marek.
Marek Kania ) (Executive VP, Managing Director and Chief Medical Officer, International)
Yeah. First question about fruquintinib data. Overall, we are very encouraged by results in our phase I study, both in cohort B and C, as you saw on the slide, which is consistent, again, mimicking almost like FRESCO study population and the other cohort mimicking FRESCO-2 population. To answer your question directly, no, it's not gonna change our timing or trajectory of our ongoing effort, obviously. As I said, FRESCO-2 completed enrollment. It's pending maturity and results.
The FRESCO-2 study is event-driven overall survival. We're expecting read out of that study in the second half of the year. Both phase I study, which you're referring to, FRESCO study completed in China led to approval in China. FRESCO-2 will be entire package, in addition to many other supporting studies.
What this, you know, phase I study is giving us really confidence and consistency across different settings and also confirms our assumptions in our FRESCO-2 study, which is very encouraging. To answer your question about commercial build, we are in a very active launch readiness mode. Actually, cross-functionally, both commercial and medical affairs teams are working as we speak very hard, and we're building up.
The 25 was actually as of last year. Currently we combined headcount, as I showed. We are 54, will be 80 plus headcount. Obviously, this build will continue. We'll continue to expand with our fruquintinib top-line results. The beauty and efficiency we have here is we are operating within GI oncology space, NET, as well as future colorectal.
There is number of efficiency and with the current existing, very strong team on both commercial and medical affairs side, which will give us great trajectory for expansions based on our decisions in the second half of the year. We feel very, strongly and positive confident that our size of organization build for future launch phase will be as much in parity with the needs of highly concentrated, you know, coverage in academic centers, but also ready to interact with healthcare professionals in the communities and the outreach NET. I hope this answer your question.
Operator (participant)
The next question comes from the line of Mike Mitchelson from Panmure Gordon. Please go ahead.
Mike Mitchelson (Director and Life Sciences Analyst)
Thanks. Hi, everyone. Thanks for taking my questions. First, it'll be a chance for you to go, Christian. Congratulations on everything you achieved with HUTCHMED, and also congratulations to Weiguo for assuming the leadership role. I just wondered on that point, given that both CEO and CSO roles are gonna be taken on by you, Weiguo, are there any organizational changes that have been made in R&D specifically to further support the CSO role? I mean, clearly it's been a dedicated sole responsibility for Weiguo to date. I just wondered, how that will potentially change organizationally.
Weiguo Su (CEO and Chief Scientific Officer)
Well, thanks for the question. We are actively evaluating several options, both internally and externally with regards to the CSO role. I think there will be organization change in the future.
Mike Mitchelson (Director and Life Sciences Analyst)
Understood. Okay. No, that's great. Thanks, Weiguo. I think I read between the lines there. I just wanted to follow on from Rajan's question, actually. I'm just wondering what the optimal global capital markets presence looks like for HUTCHMED. I'm just thinking about the proposed Shanghai listing. Given the listings already in the U.K., U.S., and Hong Kong, is supporting four global listings a realistic expectation on your side over the future?
Weiguo Su (CEO and Chief Scientific Officer)
Maybe I could say.
Marek Kania ) (Executive VP, Managing Director and Chief Medical Officer, International)
Quick. Christian, Johnny maybe.
Weiguo Su (CEO and Chief Scientific Officer)
Yeah. I'll also let Simon and Johnny mention as well. I think you know, three listings is a lot. Obviously, we've mentioned during this call that we are evaluating other opportunities as well. I think it's not realistic to go higher than three listings. I'll hand it over to Johnny and Simon to say a couple of things.
Simon To ) (Chairman and Executive Director)
Yeah. Johnny?
Johnny Cheng (CFO)
Oh, yes.
Simon To ) (Chairman and Executive Director)
Johnny, Simon is
Johnny Cheng (CFO)
Maybe you go first. Yeah. Mr. To, sorry. You go first.
Simon To ) (Chairman and Executive Director)
Yes. At the moment, you know, we don't really see any urgency to apply for Shanghai listing. I was in Shanghai recently, you know, and went to the stock exchange. They did mention that, yeah, you know, we probably don't like to see four listing, you know. At the moment, you know, we have plenty of cash. We have also alternative financing, you know, possibilities, non-dilutive financing possibilities.
There's no real urgency, you know, that we must go and get a Shanghai listing. Of course, you know, we'll look at which is the best for the shareholders, you know. Yeah. That's my answer at the moment. Johnny, you wanna say something?
Johnny Cheng (CFO)
No, I think this non-dilutive financing is probably at a higher priority for us to look into. The run rate in terms of our cash balance is more than two years, so which is average for all biotech company and which is healthy for us. With also these other ventures that we talk about potentially if we can find a good buyer for that, I think that is something that we will focus a little bit more resources on. For Shanghai listing like Mr. To just mentioned, I think we will continue to evaluate and we will not eliminate that possibility, but it is not an urgent matter for us.
Mike Mitchelson (Director and Life Sciences Analyst)
Understood. No, that's great. Thanks for your responses there, and congratulations once again.
Johnny Cheng (CFO)
Thank you.
Operator (participant)
We're now going to take the last two questions, and the next question comes from the line of John Newman from Canaccord. Please go ahead.
John Newman (Managing Director & Senior Equity Research Analyst)
Hi, good morning. Thanks for taking my question. I also wanted to add my congratulations to you, Christian, truly built one of the leading biotechnology companies in China. So congrats to yourself and obviously to the whole team. I just had one quick question really on the SYK inhibitor. Just curious if you could talk a little bit more about the timeline for global development. The reason I ask is we obviously have a few SYK inhibitors approved in the United States, but your asset has a very interesting safety profile as well as efficacy. So I'm curious about the timeline for global development. Thanks.
Christian Hogg (Executive Director and CEO)
Yeah. I'll first give you my thoughts and Marek can chime in as well. We are all very excited about the proof of concept data. China is in phase III. We are considering the U.S. and global development activities for the SYK inhibitor. We believe the data is very competitive. Now obviously with regard to timeline, I think, you know, operationally, we are mobilizing. Maybe Marek, now you can chime in and provide some more details.
Marek Kania ) (Executive VP, Managing Director and Chief Medical Officer, International)
Yeah. Thanks, Weiguo Su. John, you know, as Weiguo Su said, we were very encouraged by the profile, and we believe it can really stand out. Having said that, you know, we are aggressively focusing on execution of the expansion cohorts, which, you know, this study was a little bit impacted by our COVID limitations and slowdown in phase I.
Now we are catching up momentum. In the second half or maybe by later this year, we'll have our expansion cohorts completed. And we'll be doing data assessment and where we can take it. We have to look carefully at our data both in China and U.S. holistically, but also separately with some exposure difference.
From a regulatory strategy perspective, we have different doses in the U.S. and China. We'll be having a careful look in the next phase development. As you said, we are as encouraged as you are in the trade. At the same time, you know, at present we are taking forward our development for ITP indication as well. Overall, this program has you know, quite significant potential.
John Newman (Managing Director & Senior Equity Research Analyst)
Thank you.
Operator (participant)
The last question comes from the line of Matthew Yan from CLSA. Please go ahead.
Matthew Yan (Senior Equity Research Analyst)
Hi. Thanks for taking my question. I just got a quick one for savolitinib. Understand that the phase II trial readouts might need to come by second half this year. I wonder how we see the probability of that result if positive supporting an NDA filing overseas. Or is this more likely you would like to file an NDA after the phase II trial readout? That's my question. Thanks.
Weiguo Su (CEO and Chief Scientific Officer)
Sorry, are you talking about phase II gastric cancer?
Marek Kania ) (Executive VP, Managing Director and Chief Medical Officer, International)
No, he's talking about SAVANNAH.
Matthew Yan (Senior Equity Research Analyst)
No, no.
Weiguo Su (CEO and Chief Scientific Officer)
Savannah.
Matthew Yan (Senior Equity Research Analyst)
Savannah.
Weiguo Su (CEO and Chief Scientific Officer)
Okay. Yeah, obviously, SAVANNAH is ongoing and it's still. We believe the data is very compelling and it will be actually it certainly warrants discussion with the regulatory authorities for potential registration for conditional approval. You know, we are very happy with the level of efficacy and you know, that's why we are working with AstraZeneca to initiate the phase III, the global phase III in this patient population.
As I mentioned, you know, during my presentation that together with the data from TATTON, ORCHARD and SAVANNAH forms a great base for a strong base for this SAPPHIRE studyglobally. Particularly for the opportunity in the U.S. for conditional approval, I mean, we think SAVANNAH is very strong and we're just, you know, following the data very closely as it matures.
Matthew Yan (Senior Equity Research Analyst)
Okay, understood. Thank you very much.
Operator (participant)
If there are no further questions from Bernard, I will hand the session now back to the host.
Weiguo Su (CEO and Chief Scientific Officer)
Well, thank you very much, all, and for attending the call and look forward to working with you all in the future. Christian, you have anything else to add?
Christian Hogg (Executive Director and CEO)
I don't, Weiguo, just other than to say, you know, thanks everybody for your support through the years and, you know, I wish all the very best of luck to Weiguo and the team going forward. You know, thank you all.
Weiguo Su (CEO and Chief Scientific Officer)
Thank you very much. Thank you.
Christian Hogg (Executive Director and CEO)
Thanks. Bye-bye
Operator (participant)
Thank you. Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect.