HUTCHMED (China) - H1 2022
August 1, 2022
Transcript
Operator (participant)
2022 interim results conference call and webcast. At this time, all participants are in listen-only mode. After the conference, the speaker presentation, there will be a question and answer session. Please be advised that this call will be recorded. I will turn the call over to our first speaker today, Mark Lee, SVP of Corporate Finance and Development. Please go ahead.
Mark Lee (SVP of Corporate Finance and Development)
Thank you, Guillaume. Welcome everybody. As you know, this is our 2022 first half results. I'd like to introduce today our speakers. We will have Dr. Weiguo Su, our Chief Executive Officer and Chief Scientific Officer, Mr. Johnny Cheng, our Chief Financial Officer, Dr. Marek Kania, our Managing Director and Chief Medical Officer of HUTCHMED International, Dr. Karen Atkin, our Chief Operating Officer, and Mr. Hong Chen, our Chief Commercial Officer of China. With that, I will hand over to Dr. Su.
Weiguo Su (CEO and Chief Scientific Officer)
Thanks, Mark. Hello, everyone. As you all know, the biotech industry is going through some significant changes. HUTCHMED is trying to stay focused on our goals and objectives. During the first half 2022, HUTCHMED China commercial continued to grow and deliver strong results, particularly fulfilling considering the impact from the COVID disruptions. ELUNATE continues to gain in prescription share for third-line CRC. The lead over Stivarga continued to widen. SULANDA was included into the NRDL this year with a 52% price reduction, yet sales grew 69%, aided by much improved patient access. ORPATHYS also delivered strong sequential growth compared to second half 2021. On the pipeline, while we were disappointed by the savolitinib U.S. FDA CRL and now MAA withdrawal, our deep and broad pipeline continues to progress. Our first multinational MRCT for fruquintinib global registration will read out shortly in August.
If positive, NDA filings will begin toward the end of the year, starting from the US, followed by EU and Japan. For savolitinib, multiple registration studies, including global MRCT SAMETA for PRCC and SAFFRON for non-small cell lung cancer are enrolling. The SAVANNAH study, data to be disclosed at WCLC shortly, is also continuing to enroll with potential for filing for accelerated approval. Registration studies for our second wave of proof-of-concept products, amdizalisib, savolitinib, and tazemetostat are all enrolling. NDA submissions in China are expected during 2023 and 2024. Finally, managing changes and challenges. HUTCHMED has gone through many difficult stretches in our history. The management team is very experienced in dealing with challenges, such as our surufatinib setback or the COVID disruption in China or the overall unfavorable tech market right now.
HUTCHMED has a solid cash balance and a cash generative commercial operation in China, and we are confident we will be able to emerge from these challenges stronger. Next, I'll ask Mr. Hong Chen, Chief Commercial Officer of China, to give an update on first half China oncology commercial performance. Chen Hong?
Hong Chen (Chief Commercial Officer of China)
Thank you, Weiguo. Hello, everyone. HUTCHMED already has three in-house innovative products approved and marketed in China, and 2022 is also the second year for HUTCHMED to commercialize ELUNATE and SULANDA through its own commercialization platform. From this slide, we can see after successful NRDL renewal with only 5% price decrease, ELUNATE continued to grow strongly first half of this year. The first six months in-market sales was more than $50 million with 26% growth versus last year. By the end of May, the cumulative in-market sales of ELUNATE already achieved more than RMB 1 billion. ELUNATE already benefited more than 50,000 CRC patients. It continued to expand the leading position in third-line CRC patient share to 43% during the latest post-launch survey. Next slide, please. For SULANDA, the NRDL inclusion allows much wider patient access for SULANDA.
We can see despite 52% price cut, the value sales still increased by 69% to $13.6 million in the first half of this year, which was already over the whole year sales of 2021. The growth was up to 280% in terms of the new patient numbers treated by SULANDA. Next slide, please. This is the first year anniversary for savolitinib since it's approved in June last year. The first half of this year, in-market sales increased by 46% to $23.3 million, versus the second half of last year. As the first in-class selective MET inhibitor in China, savolitinib is now recommended for treatment of non-small cell lung cancer with exon 14 skipping in five Chinese treatment guidelines.
MET diagnostic testing is already recommended as the new standard of care for patient with late stage non-small cell lung cancer. Our commercial partner, AstraZeneca, is now proactively working on the preparation for the coming NRDL negotiation at the end of this year. Next slide, please. This slide is high level summary of HUTCHMED commercial capabilities. We can see with the team size increasing to more than 800 staff, more and more hospitals and the HCPs can be covered as well. More than 500 new hospitals were covered in the first half of this year, especially in Tier 2 and Tier 3 cities. More and highly effective promotion events executed in first half, especially through online and the digital communication to mitigate the COVID challenges.
For example, we can see we held more than 3,800 annual events with more than 100% growth versus the first half of last year. We covered more than 43,000 HCPs by SULANDA events, with also more than 180% growth. Overall, in spite of the COVID-19 challenges, we continue to make good progress to commercialize our three marketed products in China in the first half of this year. I'm very confident this momentum to continue to go from strength to strength as our commercial team continues to build over the balance of this year. Thanks. Okay, Weiguo and Marek, please.
Weiguo Su (CEO and Chief Scientific Officer)
Thanks, Chen Hong. Moving on to the pipeline progress. Our clinical development program pipeline continued to grow. Our anti-CD47 antibody, HMPL-A83, entered into Phase I study. Our first in-licensed product, tazemetostat, initiated the bridging study for China registration. Next. This slide lists 13 ongoing registration studies, both China and globally, with estimated timeline for possible NDA filings. Generally speaking, the COVID outbreak in the first half has some impact on enrollment, and we are anticipating some delay for most studies in China. Next slide. Again, the seven registration studies for savolitinib, and they are all enrolling, three globally and four in China. Next slide. This is to highlight the interim SAVANNAH data to be presented at the WCLC. The most important information, among other things, is the biomarker definition.
The data is from 193 patients, all progressed on Tagrisso with MET activation, both high and moderately high. In this study, 34% of patients were identified with high MET activation, namely IHC3+ greater than 90% of the tumor cells or MET gene copy number greater than 10. An additional 28% with moderate MET activation, IHC3+ less than 90% or GCN between five and 10 copies. As you can see, there is a clear difference in efficacy for these two subgroups of patients, including ORR, DOR, and PFS. These data supported and informed the global SAFFRON registration study, which is now underway. Next slide. In addition to targeting MET driver genetic alterations such as mutations, exon 14 skipping, or amplification, another area of strong interest is to target the immunosuppressive role of HGF MET signaling pathway.
Last year, we published the CALYPSO study in which the MET-driven PRCC patients appeared to derive robust clinical benefit from the treatment of savolitinib, durvalumab combination. Currently, the global registration MRCT is ongoing, the SAMETA study. We and our partner, AstraZeneca, are now preparing to explore the same combination in MET-driven non-small cell lung cancer. The SUN study is expected to start enrollment later this year. Next slide. Moving on to fruquintinib and its phase III clinical development outside China, let me ask my colleague, Dr. Marek Kania, Managing Director and CMO of HMI, to give you an update.
Marek Kania (Managing Director and Chief Medical Officer International)
Thank you, Weiguo. Hello, everyone. I will give you a quick update on our late phase development globally. As you can see on this slide, HUTCHMED continues to focus on colorectal cancer and really helping patients with this high burden and high unmet medical needs to find solutions. For fruquintinib, our main focus in driving that help. As you can see, this is the second most common cancer type. For second-line standard therapies, patients are running quickly out of options. Only two approved options in the third plus line is used in less than 20% of total patients. That highlights strong needs and strong rationale for fruquintinib being developed in this setting. Next slide, please.
As you've seen this slide few times in the past, last six months was our strong focus of driving our FRESCO-2, which is second pivotal study, multinational MRCT, to go through the finish line. We are actually narrowing our predictions here. We will be in position of sharing top-line results in August and presenting at upcoming medical conference for the results very soon. Just as a reminder, FRESCO-2 was discussed with all major regulatory agencies before finalizing protocol and start of the contract. Therefore, if FRESCO-2 positive, it will be key basis for our regulatory efforts both in U.S. for NDA, Europe, MAA, and Japan, as PMDA discussions.
Japan has strong participation in the study, so through this truly global effort, it will be our strong position from a regulatory point of view to start our mission. As a reminder, U.S. FDA granted fast track designation, therefore it will afford us rolling submission starting in late this year if FRESCO-2 is positive. Again, I will be talking more about FRESCO-2 very soon. Next slide, please. So far, a quick update, as we had discussions earlier in April, May about NDA complete response in U.S. I'm not going to highlight more of this. As of today, we announced withdrawal of our MAA in Europe. Main reasons are summarized in this slide, which really highlights similar concerns and similar limitations and objections from European regulatory perspective.
In addition to this, limitations in conducting inspections, both GCP and GMP, led to our discussions and decision to withdraw and focusing on path forward with both regulatory agencies to bring surufatinib to next phase development, conducting MRCT. For Japan, we are conducting a bridging study or different name for this will be pivotal study in Japanese regulatory term. We are in part two. We will be approaching PMDA for pre-NDA discussions at the conclusion of that study. Next slide, please. Weiguo, I think you will be covering this slide. Next, please.
Weiguo Su (CEO and Chief Scientific Officer)
Thanks, Marek. Now let's move on to our second wave of compounds in late-stage development, all in the HemOnc space. HUTCHMED has six assets in clinical development with several more programs in discovery. We believe this is a highly valuable HemOnc pipeline covering pretty much entire HemOnc spectrum. amdizalisib, sovleplenib, both with breakthrough therapy designation in China. Next slide. amdizalisib-Our differentiated PI3K delta inhibitor with good safety profile has continued to enroll in two registration phase two studies. The third line plus follicular and the second line or above marginal zone lymphoma. Data for other subtypes of lymphoma, including MCL and PTCL, are still maturing and will be evaluated for possible additional registration studies.
Outside China, in light of the April FDA ODAC on PI3K delta class of compounds, we are expanding patient enrollment in several subtypes to demonstrate or confirm the differentiation with a priority in post-BTKi MCL and PTCL. Let me remind you that our intention when amdizalisib was discovered was to improve upon existing PI3K delta inhibitor safety profile, which is now the center of the question. The data we published at ASH last year showed not only this promising efficacy data, but also a much more favorable safety profile, obviously need to be further confirmed in larger patient population and also in US patient population. In addition, also considering combinations such as the EZH2 inhibitor tazemetostat. Next slide, sovleplenib, the Syk inhibitor.
In China, the phase III registration study in ITP is enrolling very well with little impact from COVID, suggesting a strong unmet medical need in this patient population. Another indication where we have breakthrough therapy designation, we hope to complete enrollment of this phase III study by end of the year. Behind the ITP, 2 INDs have been cleared in China, one for autoimmune hemolytic anemia, and another for COVID-19 to explore its anti-inflammatory activity to reduce death rate in severe to critical patient population. Outside China, the dose expansion in lymphoma indications continues to enroll with a priority in Hodgkin's and post-BTK CLL. In addition, based on the encouraging POC data from the China ITP study and strong unmet medical needs in this space, we are preparing to submit an IND to explore the potential. Next slide. Our in-licensed EZH2 inhibitor, tazemetostat.
Taz is approved in the U.S. for follicular and epithelioid sarcoma indications as a monotherapy. At 2022 ASCO, the safety run-in data in combination with R-squared was presented in a second-line follicular lymphoma. The efficacy and safety were very encouraging. Together with our partner, Epizyme, the global phase III study, the SYMPHONY-1, has been initiated in second-line follicular comparing R-squared plus Taz versus R-squared. China will be part of the global MRCT to support China registration. In parallel, we just kicked off the bridging study in China to support initial registration of tazemetostat as a monotherapy. Taz has been approved in Hainan province in China through a special registration pathway based on the U.S. approval. Multiple combination proof of concept studies are also being planned. This update on the late-stage assets.
Next, I'll ask Johnny Cheng, CFO, to give us an update on the financials. Johnny?
Johnny Cheng (CFO)
Thank you, Weiguo. Moving on to the next page, please. As of June, company maintains a strong balance sheet. We have cash and short-term investments of over $800 million, unutilized banking facilities of over $170 million. In addition, we have another $58 million cash in our joint venture with Shanghai Pharmaceuticals. Overall, our target is to extend the cash run rate to three years. Move on to the next page. The strong performance of our commercial teams resulting group revenue up by 28% to over $200 million, of which our oncology business revenue increased by more than double of last year's to over $90 million. We continue to increase our investment in R&D to over $180 million in China as well as in the U.S. and Europe.
The profitability of our equity invested investees increased by 17% to over $33 million. Moving on to the next page, please. Our non-core assets continue to do well. As you all can see, it has contributed more than $ half a billion net income to the group. We continue to explore ways to unlock the value of these assets. To provide additional cash resources to support our R&D investment. Moving on to the next page. As you all have heard from Hong Chen earlier, with our strong performance, commercial performance, we will maintain our guidance to the market we gave earlier. That is $160 million-$190 million for our oncology and immunology business. I will now pass on to Weiguo.
Weiguo Su (CEO and Chief Scientific Officer)
Okay, thanks, Johnny. To recap, while the macro environment continues to change, HUTCHMED strives to stay focused on our commercial operations and pipeline progression. We expect that the strong momentum in China commercial to continue in the second half. On the pipeline in China, we continue to expand the life cycle indications behind our three approved products through fruquintinib, surufatinib and savolitinib. At the same time, moving our second wave of drug candidates, amdizalisib, sovleplenib and tazemetostat towards registration. Outside China, while surufatinib has been a disappointment, we believe it is a unique case and won't have any significant impact on the rest of the pipeline.
We do have a deep pipeline and a robust registration strategy, starting from fruquintinib, for which a multinational MRCT will read out shortly in August and NDA filings, if positive, in the U.S., EU and Japan, starting from the end of the year. Amdizalisib and sovleplenib are both generating POC data and will be engaged with the FDA to discuss and define the registration pathway in the next six to 12 months. Finally, I would like to point out that even though we have a solid cash balance, we are prepared to manage through potentially long-lasting unfavorable equity market. We are reviewing our clinical programs and operations carefully to make sure that we spend cash prudently. We will also look to grow our China business further to generate more income. Finally, we plan to up our efforts in licensing and collaboration activities. Our current environment is challenged.
We are confident that we will be able to leverage our well experienced management team and emerge from the difficult period even stronger. This is not the first time that we have managed through difficult market conditions. This wraps up our presentation. The management team will be happy to answer any questions.
Operator (participant)
Ladies and gentlemen, we will now start our question and answer session. If you wish to ask a question by phone, please press zero one on your telephone keypad to enter the queue for the question and answer session. To cancel the queue, please press zero two. We have some questions coming in. The first one comes from Kelly Shi from Jefferies. Please go ahead.
Kelly Shi (SVP and Senior Equity Research Analyst)
Congrats on the progress, and thank you for taking my questions. Regarding the regulatory pathway for fruquintinib in the U.S. based on a global phase III FRESCO trial, a U.S. phase I trial, and a FRESCO China trial, which should provide comprehensive clinical information. Given the experience with surufatinib, do you see any potential issues regarding the applicability to the U.S. patient population? And also, like, to the current U.S. medical practice of the potential data package to support U.S. approval in CRC. Was this a topic of discussion from the previous U.S. FDA meeting? Thank you, and I also have a follow-up.
Weiguo Su (CEO and Chief Scientific Officer)
Okay, thanks, Kelly. Well obviously, you know, the strategy for fruquintinib registration in the U.S. and elsewhere for that matter obviously will be centered on the FRESCO-2 study, which is obviously MRCT and in representative patient population. I think the China study, the original FRESCO study and also all other early stage clinical studies will serve as supports. We don't expect any issues. We certainly had previous discussion with the agency as well, before we actually kicked off the FRESCO-2. No, we are actually quite confident that this MRCT should cover most issues. It's you know, completely different from the surufatinib case. Maybe Marek, if you want you have anything else to add?
Marek Kania (Managing Director and Chief Medical Officer International)
Yeah, Weiguo, thank you. You know, I would just add my voice of confidence, you know, and as you said as well, FRESCO and fruquintinib case has nothing to do with surufatinib case, which is unique. We had numerous formal discussions with US FDA in the end-of-phase II meetings, Type C meeting. We were very transparent in, and FDA was very collaborative in the way how we designed this FRESCO-2 study, which is main pivotal study. FRESCO-2 will be considered in the totality of the package as well. We are very confident if FRESCO-2 is positive, that would be based on three continental regulatory discussions.
We already reported before, we have also signed scientific advice with EMA, which provided comments to the FRESCO design. For Europe, FRESCO-2 will be a primary pivotal study. At the same time, we had the same discussion with PMDA, so we remain very confident in our strategy here.
Kelly Shi (SVP and Senior Equity Research Analyst)
Great to hear. Thank you very much. I also have a follow-up regarding the PI3K inhibitor. How should we think about the market opportunity in the lymphoma indications in the China market, given CD19 CAR Ts and also CD20 bispecific antibodies have entered the market and there are also a few entering the market. How different is the competitive landscape in China versus in the U.S. for those lymphoma indications? Thanks.
Weiguo Su (CEO and Chief Scientific Officer)
Yeah. You know, obviously it all comes down to the safety and tolerability. If proven safe and efficacious, we believe PI3Kδ should have a very strong competitive edge because it can be used before or after these biologics treatment, and also it's oral. As you know, these are relatively indolent diseases and patients will have to stay on treatment for a very long time. Safety and tolerability is extremely important. Now some of the bispecifics have shown some strong data, but again, these are all single-arm studies and still remain to be confirmed. CAR Ts work, you know, it can work for some patients, but not for all.
You know, even patients benefit, they ultimately progress or have recurrence. All in all, we believe indolent lymphoma patient population, it's a big population and patients live for a long time, and they need to rotate to new therapies repeatedly. A good efficacious and safe tolerable PI3Kδ inhibitor, we believe, has its place for these patients.
Kelly Shi (SVP and Senior Equity Research Analyst)
Very helpful. Thank you.
Weiguo Su (CEO and Chief Scientific Officer)
Thanks.
Marek Kania (Managing Director and Chief Medical Officer International)
Operator, maybe you can move to the next.
Weiguo Su (CEO and Chief Scientific Officer)
Operator.
Operator (participant)
Hello, Paul Choi from Goldman Sachs. Your microphone is open.
Paul Choi (Senior Equity Research Analyst)
Thank you. Good evening, and thank you for taking our questions. Just a couple of quick financial ones to start, and then one pipeline question. First, was there any inventory build at the end with regard to some of the newer products that were included on the NRDL? And then with respect to the guidance being maintained, can you maybe speak to how you view the current macro environment and what would sort of be the pushes and pulls that might drive your full-year results to the lower end versus the higher end? And then I had a pipeline question to follow up.
Weiguo Su (CEO and Chief Scientific Officer)
Yes, Paul. You know, with regard to the inventory, you know, we believe it's at the moment, it's a normal inventory level. If anything, during the lockdowns, from April, May and into June, there was some kind of depletion, some level of depletion of inventory. At the moment, we think it's at the normal level of inventory and, you know, we are quite confident the second half, you know, we think the momentum will continue.
With regard to the push and pull, you know, again, we are a bit concerned about the COVID-19, whether it can, you know, have another outbreak somewhere else or somewhere, and you know, it can be quite disruptive, basically. That remains a bit uncertain. You know, nobody can predict the situation. Although we have been, you know, gone through once and we, Chen Hong's team is putting in place multiple measures, including the online doctor's visit, online conferences, and also the inventory and distribution management. We believe we are now better positioned to deal with any potential COVID outbreak in China or potential lockdowns.
Nevertheless, you know, it can be an issue depending on the scale, obviously. You know, we are cautiously optimistic that we'll be able to deliver within the guidelines and hopefully we can do better towards the higher end. I think the only pull, or you know, the headwind would be the uncertainty of COVID.
Paul Choi (Senior Equity Research Analyst)
Okay. Thank you for that. As a follow-up, my pipeline question is, I know you'll have the FRESCO-2 results imminently here in August. Is there a plan to present the data more in detail at a medical meeting here in the second half of 2022, or will we have to wait until 2023? Thank you for taking our questions.
Weiguo Su (CEO and Chief Scientific Officer)
Yeah. Marek, if you want.
Marek Kania (Managing Director and Chief Medical Officer International)
Yeah, I can take it. Paul, obviously our principal is, you know, disclosure of important data, both in an announcement level, expeditiously, but also in a full data set as quickly as possible at the major conference. I'm not here in a position to confirm which conference. You can go and speculate, but our aim is always as soon as possible at the major conference, but obviously short of being accepted and confirmed. We'll have separate announcement when we have exact location and timing for that. It will be definitely this year.
Paul Choi (Senior Equity Research Analyst)
This year. Okay. Thank you very much.
Marek Kania (Managing Director and Chief Medical Officer International)
This year. Yeah.
Operator (participant)
We have another question from Mike Mitchell from Panmure Liberum. Please go ahead.
Mike Mitchell (Senior Healthcare Research Analyst)
Thanks. Good afternoon, everyone. Many thanks for taking my questions. I just have a couple. I just wondered in terms of the current commercial organization, you know, you're continuing to add significantly to the oncology team. I think you said you're over 800 people now. The number of oncology physicians covered is starting to flatten off somewhat. I just wondered how optimal the commercial organization now looks just in terms of structure. A question on fruquintinib and the sort of global strategy. Clearly, the FRESCO-2 data is important in terms of paving the way towards the regulatory process outside of China and more widely also for the global strategy for the business.
If that doesn't play out as we hope, then I think you're probably then looking at the global savolitinib studies, SAMETA and SAFFRON, to progress the global story, which are a little way out in terms of potential NDA. I just wondered if you could recap the tazemetostat global plans in that context, please. Thanks.
Weiguo Su (CEO and Chief Scientific Officer)
Okay. Thanks, Mike. With regard to the commercial organization in China, we are now around 800 staff. We believe this is the optimal scale for the current portfolio of products. We don't intend to grow, you know, further. However, we instead will focus on driving efficiency and driving productivity from the current staff. You know, with regard to your second question on the fruquintinib global registration, I think, you know, it. There can be all kind of scenarios, but first things first, we need to wait until the FRESCO-2 data to read out.
Personally, I'm you know just like you all anxiously waiting for the FRESCO-2 to read out. I think fruquintinib we have accumulated a wealth you know amount of data that this global MRCT should serve as a pivotal. I don't know if Marek you want you have anything else to add?
Marek Kania (Managing Director and Chief Medical Officer International)
No, you said it well. Obviously, given proximity of the outcome, obviously we are thinking like all of you about positive, negative outcome. Given the wealth of data, including one positive study in addition to number of other studies, our cohorts from the U.S. studying across different lines of prior therapy with the consistency of results and clinical benefits demonstrated, there's nothing to make us, you know, concerned about anticipation. We are doing studies for a reason and, in the normal circumstance, you know, you do first pivotal study, you are approximating 70%-80% probability of success in any study. Given our already one positive study, we are confident.
Again, let's cross the finish line and we are planning for success for now, but obviously we'll adjust, you know, accordingly if in the case the negative outcome was surprise. Science is science.
Weiguo Su (CEO and Chief Scientific Officer)
Okay. That's fair.
Marek Kania (Managing Director and Chief Medical Officer International)
I think next one was related to in the wake of post-savolitinib global, maybe that angle of question. Do you want to address?
Mike Mitchell (Senior Healthcare Research Analyst)
Well, obviously, you know, post the FDA CRL and also considering the recommendation of MRCT. Are you talking about surufatinib or?
Marek Kania (Managing Director and Chief Medical Officer International)
No, Mike. No, no. I think question was in case of negative fruquintinib, will our focus shift entirely to savolitinib global development, from that perspective? I mean, it's both programs are important, correct.
Weiguo Su (CEO and Chief Scientific Officer)
I think, you know, obviously if negative, it will be a major setback, right? I mean, it's just similar to surufatinib, right? Post the CRL. It obviously will remain, you know, we remain confident that these are valuable drugs that can help patients. But the setback is, you know, basically is a timeline. It's gonna push back, you know, significantly years into, you know, we are talking about three, four years for the first approval. You know, we'll evaluate very carefully, similar to what we are doing for surufatinib. We'll be doing the same for fruquintinib if negative.
Again, you know, the NPVs can change greatly if you know, if the timeline continues to be pushed back. That's an area we need to be very careful.
Marek Kania (Managing Director and Chief Medical Officer International)
Understood.
Mike Mitchell (Senior Healthcare Research Analyst)
That's right, guys. Thank you.
Weiguo Su (CEO and Chief Scientific Officer)
Yeah.
Operator (participant)
Next question comes from Yang Huang from Credit Suisse. Please go ahead.
Yang Huang (Vice President and Equity Research Analyst)
Yes, this is Yang Huang from Credit Suisse. Thanks for the opportunity for me to ask question. The first one, actually, I just want to have a follow-up on FRESCO-2. I know some of my peers already asked about this study. I think, given the study actually, trial started in, I think, second half of 2020. However, we all know FDA certainly changed their position into reviewing drugs from China in 2021. It will be very, very helpful if we can get some more colors about what kind of communication we had before we started the FRESCO-2 study with FDA. What we talk about with FDA before we started the FRESCO-2's trial?
I will note, have the company noticed any kind of potential change in FDA's view after 2021 events? Thanks. I have a follow-up on financial too.
Weiguo Su (CEO and Chief Scientific Officer)
Yeah. I think we already touched on this. Now, obviously we had end of phase II or pre-phase III discussion with the U.S. FDA and it got aligned on the study design for FRESCO-2. You know, if positive, obviously we'll have another opportunity to, you know, for a pre-NDA discussion likely. Also note that this particular indication, we have fast track designation and we can, you know, discuss it with the agency basically any time. With regard to FDA kind of position, you know, I'll ask maybe Marek to chime in.
He obviously has, you know, more involvement and discussions with the FDA. Marek?
Marek Kania (Managing Director and Chief Medical Officer International)
Yeah. Thank you, Yang. Yeah, and just to clarify, yes, I simply hear some confusion in the system here. You know, overall challenges with surufatinib or and any other sponsors related in this situation was related to agency concern, where application to NDA is made with one country phase III trial or phase III trials. That's the core of their concern, bringing one country and if China, non-China, it's just even broader. If you would bring to one country specific, not necessarily applicable to U.S. populations. That's the core of their concern. The FRESCO-2 is very different case or fruquintinib is very different case. As Weiguo Su said, we had pre-NDA, pre end of phase I meeting or pre-phase III meeting.
We had another Type B, very similar meeting this year, and we are preparing for Type C meeting, very shortly, post top line results. So far, agency has been very consistent, and therefore again, important fact is we are running global study. Global study conducted in 14 countries, 150 sites and U.S. is contributing to this study in a significant way. It cannot be more than multinational, more than regional study. It is exactly what agency is expecting. Every other study supporting or part of the package will play important role as well. Yeah, don't overplay that. Overall, you know, confidence will still happen into everything else moving forward because it's not the same.
Yang Huang (Vice President and Equity Research Analyst)
Thank you, Weiguo Su.
Weiguo Su (CEO and Chief Scientific Officer)
Okay, got it.
Yang Huang (Vice President and Equity Research Analyst)
Yes, thank you. My second question is on our financials. We noticed in the first half our total revenue has a pretty good growth. I think growth about 30%, but the cost of revenue only grew, I think, at 10%, much slower than our total revenue growth. Do you think the trend is going to continue? Or what caused this kind of slower growth for the cost of revenue in the first half this year?
Weiguo Su (CEO and Chief Scientific Officer)
Okay, thanks for the question. I'll ask Johnny to provide the answer.
Johnny Cheng (CFO)
Okay, thank you, Weiguo Su. I think it's the composition of our products. If you compare to the last period, we did not have savolitinib in the first half, which we now have savolitinib in our first half of this year. As you all know, we recognize for savolitinib in-market sales, we actually recognize 30% of the royalty. So that actually improve in terms of our gross profit margin. On the other hand, of course, we have invested into our sales force, which a part of which we capture in the cost of sales. Combining all together, the product actually makes a difference to this, the analysis that you just referred to.
Going forward, I think we will continue. Hopefully, I think we are targeting to continue to do well in ELUNATE and surufatinib. At the same time, I think the proportion of savolitinib sales should increase over time. I hope that answer your question.
Yang Huang (Vice President and Equity Research Analyst)
Okay. That's very helpful. Thanks.
Operator (participant)
Next question comes from Louise Chen from Cantor. Please go ahead.
Wayne Wu (Equity Research Associate Healthcare)
Hi, this is Wayne Wu for Louise Chen, and thank you for taking our questions. Our question is on surufatinib. The EMA indicates that these studies were not representative of patients and medical practice in EU, so why do you think this wouldn't be a potential complication in Japan? And just to clarify, will you still pursue global path forward to surufatinib in light of the US and EU need for local trials? Thank you.
Weiguo Su (CEO and Chief Scientific Officer)
Well, I think, you know, it's understandable that that particular argument is almost identical from U.S. CLL, which is the patient representative patient population. I think in Japan it is quite different. First off, obviously, they are Asians, right? And secondly, it's on a different registration path. They requested us to do a bridging study, so that study is ongoing. And obviously we'll, you know, we'll continue to discuss with the PMDA in Japan. And clearly, I think it's understandable between Asian and Caucasians, in terms of patient population difference. Japan, you know, the they are Asians, but but they also on a very different registration path.
Anything else to add, Marek?
Marek Kania (Managing Director and Chief Medical Officer International)
No, I would only add or highlight, we called surufatinib kind of case as a unique case, and actually Japan case will be as unique as it can be. I don't recall personally two Phase III studies coming from China with attempt for NDA submission in Japan for high unmet medical needs. As Weiguo Su said, with bridging study, phase I will engage post conduct of this study, which we expect in 2023, and discuss path forward in the pre-NDA discussion. We'll see. As you know, Japan always also look at NDAs approval in U.S., so there may be some bias persistence in that context.
We'll cross the bridge when we have the data.
Wayne Wu (Equity Research Associate Healthcare)
Got it. Thank you.
Operator (participant)
Next question comes from Matthew Yan from CLSA. Please go ahead.
Matthew Yan (Healthcare Analyst)
Hi, management. Thanks for taking my question, and congratulations on the results. I've got two questions regarding savolitinib. First is that I noticed on your presentation material, you mentioned that you filed the NDA based on SAFFRON in 2025. Does this mean that the SAVANNAH data will not support an NDA filing in the near term? My second question is regarding SAVANNAH readout, because just publishing, how will you see this help savolitinib differentiate in terms of its clinical profile versus peers that are already approved like capmatinib and tepotinib? Yeah, those are two of my questions. Thanks.
Weiguo Su (CEO and Chief Scientific Officer)
Okay, thanks. Thanks, Matthew. Well, the SAFFRON NDA's timeline, 2025 is obviously an estimate. I think it will. We just got it started, so it all depends on the enrollment speed and also the PFS follow-up, which, you know, sometimes it can be longer than what we expect. But the SAVANNAH, I think we probably have more clarity, right? And obviously we need to get aligned with the U.S. FDA on the potential to, you know, for savolitinib, SAVANNAH study to support an accelerated approval.
We think our, you know, both HUTCHMED and AstraZeneca, our assessment is that SAVANNAH can be at least at the approval timeline 12-18 months ahead of SAFFRON in the U.S. Now, your second question on the differentiation with the tepotinib and others. Now, I think obviously we have not. You know, these two compounds, tepotinib and capmatinib, they're not approved in China yet. They've been exposed to very, you know, limited number of Chinese patients. Just looking at the profile, I think, you know, they're all potent and selective c-MET inhibitors. However, they're very, you know, they vary significantly in terms of the chemical structures.
I would expect differences in pharmacokinetics or in compound-based safety profile. You know, because they have limited exposure in Chinese patients, it's hard to tell, you know, the difference. You can't compare from study, you know, from the Chinese study versus tepotinib or capmatinib studies outside China. With regard to other studies, I think, you know, clearly, AstraZeneca has osimertinib and they know the patients very well. Now we have the biomarkers figured out.
We think we are, you know, we have a pretty good competitive edge over the other two products in terms of the EGFR TKI-refractory patient population. In other studies, I think we have the only combination in PRCC. I think savol is the only compound now exploring gastric as well. I think we have a much broader, you know, program than the other two. I think the challenge with MET is it's very fragmented.
It has multiple types of driver genetic alterations, including point mutations, exon 14 skipping, amplification and fusion and so forth. They all require different diagnostics to support, and just very tedious to do, you know, because of low incidence and difficult diagnostics. You know, at least AstraZeneca and HUTCHMED, we have made good progress in non-small cell lung cancer, gastric, and PRCC. I'm sure there are multiple other tumor types such as, you know, CRC for instance, head and neck as well, yet to be explored.
Operator (participant)
Okay. That's very clear. Thanks, Dr. Su. We have another question from Alec Stranahan from Bank of America. Please go ahead.
Speaker 12
Hey, guys. Good morning. Thanks for taking our question. This is John. I'm on for Alec. Kind of a two-part question from us. On the FRESCO-2 trial, through your conversations with the U.S. regulatory agency so far in your experience, you know, how do you think they're gonna be more or less viewing the data? Are they going to view it in kind of the grander landscape of the current U.S. biologic market, or are they going to kind of also look into a comparison with the FRESCO-1 Chinese trial? That's the first part.
Just to build off of that, if they do look into the comparison with the initial FRESCO-2 Chinese trial, do you think that they will be factoring the fact that an MRCT with a harder to treat population in the U.S. and international landscape will potentially be a factor at play? That's my question. Thank you.
Weiguo Su (CEO and Chief Scientific Officer)
Yeah. I think that's a really good question. I think yeah, I'll have a brief response, and then Marek can chime in. You know, the FRESCO versus FRESCO-2, obviously these are very different studies, right? Different patient population and different prior therapies. But they both have merits, and they can support each other. That I think that's my initial read on this. I think the FRESCO and all other Chinese studies will form the basis to support the FRESCO-2, both in terms of efficacy in different patient population, in different settings or subsets. You know, with or without prior VEGF, you know, VEGF or VEGF treatment. You know, China or Chinese versus Caucasians, you know.
I think that they will complement each other basically. That you know, maybe Marek now you can add further your comments on this.
Marek Kania (Managing Director and Chief Medical Officer International)
Yeah. I guess it's a good question, John, but obviously one statement I will make, obviously, cross-study comparisons are very risky and obviously not scientific, although everyone is doing this as you know. FRESCO-2 study is designed to address uniquely and independently questions designed and built in the study. Study is highly powered, 90% power to detect primary endpoint. Obviously, if positive, this study could stand alone with FRESCO or without FRESCO. But in totality, we always look at the totality of the data. So far we haven't seen any sort of big discrepancies in you know, prior lines of therapy. As I mentioned before, we conducted a number of cohorts with heavily pretreated in our US study. Actually, one cohort was mimicking exactly FRESCO-like. One was mimicking like exactly FRESCO-2 populations for more heavily pretreated.
We see consistency in the clinical benefits. I mean, I'm not going to speculate here, but FDA, if you're asking me for more precise answer here, we had those discussions and study design for FRESCO-2 is, pivotal study. If positive, it will do the job, obviously, and we'll use totality of the data to put the most convincing package. That's the reason why, most clinical investigators and really thought leaders in the field are very strongly supportive of this study. That's why the study also accrued in almost record time, 14, 15 months during COVID limitations. I will stop here.
Operator (participant)
Okay. Thank you. Thank you for the call.
Weiguo Su (CEO and Chief Scientific Officer)
Okay, thanks.
Marek Kania (Managing Director and Chief Medical Officer International)
Sure.
Operator (participant)
It was our last question. Ladies and gentlemen, dear speakers, I give you back the floor for the written questions.
Mark Lee (SVP of Corporate Finance and Development)
Hi, it's Mark. I have some written questions, so I will read them out. On the online system we have several questions. The first is regarding the Holding Foreign Companies Accountable Act, as several companies have appointed U.S.-based auditors, does the company have an update on this issue? Regarding amdizalisib, has the China regulatory authority raised any concerns regarding single arm design? Would management also share the dose selection strategy? Weiguo?
Weiguo Su (CEO and Chief Scientific Officer)
Yeah. At the moment, we've had multiple regulatory interactions with China CDE and the two registered single arm studies are ongoing and without modification. With regard to dose in the China study, it's 30 mg QD flat dose without any dose modifications, basically. I mean similar. You know, like, as you know, I guess parsaclisib and zanubrutinib, these compounds modify their dosing regimen throughout the study. Amdizalisib can be taken basically at 30 mg QD flat and continuous.
Mark Lee (SVP of Corporate Finance and Development)
Okay. Thanks, Weiguo. Maybe I can direct this question at Johnny. In the past or the question is, what is the funding mechanism for the factory? How do we budget a factory?
Johnny Cheng (CFO)
Thank you, Mark. For the factory, in terms of, I'm reading the question also. The question is, how we fund the factory in terms of the total cost of the factory and so forth. We mentioned earlier, the total project for the new factory in Shanghai is about $130 million.
We have so far spent about $30-odd million. This year we target to spend $60 million, but we have a fixed asset infrastructure loan with the local bank in China, which is structured for 10 years, for the arrangement of payback and the drawdown of this loan. The entire factory will be drawn out of this fixed infrastructure loan provided by the local bank. The total amount is $130 million. The project we target to complete by next year, end of next year. Within this year and next year we will be drawing down, slowly drawing down the required amount for this CapEx.
Mark Lee (SVP of Corporate Finance and Development)
Okay, thanks. Johnny, perhaps I could ask you to answer the question on HFCAA as well.
Johnny Cheng (CFO)
Sorry, the question before was related to some of the other companies have changed their auditor, U.S.-based auditor.
Mark Lee (SVP of Corporate Finance and Development)
Okay.
Johnny Cheng (CFO)
To our circumstances, it is different to other companies and some of these companies. For us, majority of our operation assets, revenue generated, business are all based in China. Even by changing the auditor to a U.S.-based auditor, we will not meet the requirement as those are U.S.-based auditors, they are not qualified to have license to audit in China, and therefore they would not be able to provide the supporting documents to the PCAOB. We continue to monitor this progress of the development between the authorities of the two countries. In the meantime, I think everybody knows our listings in Hong Kong and U.K. shares are fungible with the U.S. ADS. Thank you, Mark.
Mark Lee (SVP of Corporate Finance and Development)
Okay, thank you, Johnny. Okay, there's another question. Just, does the takeover of Epizyme by Ipsen change anything for development of tazemetostat?
Weiguo Su (CEO and Chief Scientific Officer)
We don't think so.
Mark Lee (SVP of Corporate Finance and Development)
Yeah.
Weiguo Su (CEO and Chief Scientific Officer)
No, we don't think so.
Mark Lee (SVP of Corporate Finance and Development)
Okay. Thanks. I think that's. I think we're running out of time now, so maybe we need to draw a line here. Well, Weiguo, do you have any closing remarks?
Weiguo Su (CEO and Chief Scientific Officer)
No, just wanna say, you know, we continue to focus on the execution and we look forward to a good second half, you know, hopefully starting from, I think the most important is the FRESCO-2. You know, we'll be in touch basically.
Mark Lee (SVP of Corporate Finance and Development)
Okay. Thanks, Weiguo. Thank you everybody for joining the call.
Weiguo Su (CEO and Chief Scientific Officer)
Okay. Thank you.
Johnny Cheng (CFO)
Thank you.
Operator (participant)
Ladies and gentlemen, this concludes today's conference call. Thank you all for participating. You may now disconnect.