HUTCHMED (China) - Earnings Call - H2 2024

Transcript

Operator (participant)

Welcome, everyone. Thank you for joining HUTCHMED 2024 Full Year Results Call. Everyone is on listen-only mode at this stage. We will first start off with a presentation, and then we will have a Q&A at the end. You can actually enter your question in the Q&A box at the very bottom of your screen, or you can also press the raise hand button where we will call your name, and then you can ask the question.

This information in the presentation will be also on our homepage where you can download the PowerPoint presentation as well. Should you experience any technical difficulties, please send a chat message in the chat box. This session will also be recorded, and the recorded webcast will be posted on the platform in about a day or so.

Just to go over some of the safe harbor statements, the performance and results of operation of HUTCHMED contained within this presentation are all historical in nature, and past performance is no guarantee of future results. Forward-looking statements are based on current beliefs and expectations of management regarding future events and are subject to significant known and unknown risks and uncertainty.

Should one of these risks materialize, then the assumption may be proven to be incorrect, and actual results may vary from what was mentioned in the forward-looking statement. Today, we will have a very good lineup of presentations. First, our Chief Executive Officer, Chief Scientific Officer, Dr. Su, will have the opening, and then our Chief Financial Officer, Johnny Cheng, will go over the 2024 financial review and outlook.

Our Head of Commercial, George Yuan, will go over our commercial aspects, and that will be followed by our Head of R&D and Chief Medical Officer, Michael Shi, to talk about our pipeline updates and also our new ATTC platform. We will be followed by a closing remark by Dr. Su, and then we will have the Q&A. Without further delay, I will pass over the presentation to Dr. Su.

Weiguo Su (Executive Director, CEO and Chief Scientific Officer)

Okay, thank you, David. Good morning, good evening, everyone. Welcome to HUTCHMED Results Conference Call. Today, we announced 2024 full-year results. We are pleased and proud to report a net profit for 2024 behind the global commercial success of FRUZAQLA. The management will share more details on the 2024 results and provide an update for 2025. Overall, financially, FRUZAQLA did exceptionally well with total sales of $290.6 million.

On the pipeline, we saw savolitinib full approval in China, with expansion into the first line for exon 14 skipping non-small cell lung cancer. Globally, savolitinib SAVANNAH/SAFFRON studies progressed well, positioning as well for potential global registration. Towards the end of 2024, we reported positive SACHI interim analysis in China in second-line EGFR mutation-positive MET-amplified non-small cell lung cancer patients, leading to NDA submission before the end of 2024.

For fruquintinib, towards the end of the year, we received approval for second-line endometrial cancer in combination with sintilimab. We believe these new indications and new approval of new products will help drive China commercial. 2025 is shaping up a big year for the pipeline.

Michael will go through the details with you. Looking forward, we are starting to get excited about our next-generation innovations, and these are ATTCs now starting to move towards clinic. The success of these programs will ensure our long-term growth beyond 2030. With that, let me invite my colleague, Johnny, our CFO, to go through the results. Johnny, please.

Johnny Cheng (Executive Director, CEO, and CFO)

Thank you, Dr. Su. Yes, we end the year with cash resources of over $830 million, which reflects a small reduction of around $50 million from 2023. A portion of the use of the cash resources was utilized for our long-term incentive plan to retain talents. Another portion was attributable to working capital to support our ex-China collaboration with Takeda.

Moving on to the next page. On the financial results, we recognized consolidated revenue of $630 million and reported a net income of $37 million. Our oncology business revenue met our guidance last year to achieve over $360 million revenue. Overall profitability was the result of strong commercial performance, ongoing recognition of deferred revenue, tight control over selling and admin expenses, as well as scaling down our ex-China R&D operations from the restructuring initiatives we started in 2023.

On the right-hand side of the page, as you can see, the 2025 revenue guidance for our oncology business is $350 to 450 million. As compared to last year, this guidance has taken into account the non-recurring service and manufacturing income from Takeda to support regulatory approval and also commercial launch in various jurisdictions in 2024. I will now pass on to our Head of Commercial, George Yuan.

Weiguo Su (Executive Director, CEO and Chief Scientific Officer)

Thank you, Johnny. If we look at the commercial side, the overall HUTCHMED Oncology portfolio delivered a very solid performance with $500,000,000 sales, which is in-mark sales, and more than double of the sales of 2023. The growth is mainly driven by FRUZAQLA, as our CEO mentioned, and also Elunate and Sulanda continue to deliver a growth in a very complicated market environment.

Orpathys is a little bit flat with more competition to the market. As everyone knows, now there's five MET inhibitor in the market nowadays. In 2025, we'll continue to look for an ambitious target with more than 30% growth for our combined portfolio. Next slide. If you look at the FRUZAQLA, the 2024 is the first full-year performance commercialized by Takeda outside China.

Of course, the US played a dominant role for the success, but within the 12-month period, the FRUZAQLA got approval in 12 countries. We also believe the market in Europe, once the major market in Europe, once they get a reimbursement, the growth will further be driven. Also, the international guideline being supported by the brand for the growth. For Japan, with Takeda's experience in the GI, especially with previous experience with Vectibix, we have a high expectation as well.

Next slide. In Elunate in China, we know that China is an aging population, and with the lifestyle change, the CRC is now a leading cancer type in China. Anti-VEGF treatment is well adopted in the later line treatment of the mCRC. Elunate achieved $115 million in 2025 and still keeps the third line mCRC market leader position with very strong data and the guideline support.

Of course, the market becomes more and more complicated, and also the competition becomes severe with more recommended generics going to the market, and also the tests were to get reimbursement. In December 2024, Elunate received its NMPA second-line approval, and this is bringing the VEGF-TKI combo with PD-1 into the gynecology market and will further drive our growth in the future.

Next slide. We shift the gear to talking about neuroendocrine tumors, which is a relatively neglected area in the oncology community due to the low incidence and widely distributed in various organs across the body. Recently, with more medical education in which HUTCHMED played a critical role that received a lot of attention by the oncologists, and Sulanda, with its differentiated profile, became the leader of the TKI and continued to gain market share according to the IQVIA survey.

In 2024, Sulanda continued to deliver double-digit growth. Of course, on the flip side, we see a lot of players coming to the market, especially you see the new SSA coming to the market, as well as a lot of new medicines under development. Let's talk about ORPATHYS. ORPATHYS is the first MET inhibitor being approved in China, and we are proud that ORPATHYS really changed the MET alteration in cancer patients' lives in China.

In 2024, there are four new players, both from local and from multinational, into the market, especially when we received an NRDL coverage for the first line, while ORPATHYS is still the second-line coverage. With AZ's commercial capability in the cancer area and also wide coverage, ORPATHYS withholds the sales number and continues to penetrate the vast China market.

We believe the full approval of first-line and the reimbursement listing afterwards, plus the potential business opportunity to combine with TAGRISSO for MET amplification patients, will regain the momentum of the brand. Thank you. Now let's shift to Michael.

Johnny Cheng (Executive Director, CEO, and CFO)

Yeah, thank you, George. Good morning, good evening, everyone. I'm giving you a pipeline update. We have made tremendous progress on our late-stage products. In addition to global approval in CRC, fruquintinib is also expanding into new indications in endometrial cancer and RCC. Two other compounds, savolitinib and surufatinib, are also in late-stage development in multiple indications. Our second wave of hematology products, sovleplenib and tazemetostat, are all at NDA stage and the registration trial for new indication development.

I want to bring attention to our third wave of products, fanregratinib, our FGFR inhibitor, and the enasidenib IDH1 and 2 dual inhibitor, are also at the pivotal trial stage to propel future growth. Next slide. On the life cycle indication development, we received the conditional approval in China for the fruquintinib plus sintilimab in the treatment of second-line endometrial cancer.

EMC indicated the incidence, the mortality of projected growth in China, and the patients who progressed on the first-line therapy remained with a high unmet need. The pivotal trial, FRUSICA-1, we have presented data in ASCO 2024. The combination for fruquintinib and sintilimab showed meaningful efficacy and manageable safety profile.

The overall response rate in 87 efficacy evaluation patients was 35.6%, including two complete responses, and the DCR was 88%, and duration of response was now reached. Also, the median PFS was 9.5 months, and the median survival was 21 months. After now, the most common therapy option for second-line endometrial cancer is the chemotherapy. The fruquintinib and sintilimab combo are the new chemo-free regimen. This group patient is very high on unmet need. Okay, next slide. Increased mortality rate and renal cancer in China also outpaces other developed nations.

The second-line treatment option remained very limited in China. FRUSICA-2 is a phase III result in the second-line RCC with fruquintinib plus sintilimab versus axitinib or everolimus as a comparator. I am very pleased to report that today, earlier, we announced the positive top-line results for FRUSICA-2 trial, and an NDA preparation is planned. If approved, this will be the first immune checkpoint inhibitor and TKI combo in China for the second-line RCC.

I am very excited to report this in the upcoming scientific conference. Next slide. In partnership with AstraZeneca, we are making great progress on savolitinib global and China development. These are the late-stage trials, three led by AstraZeneca and four led by HUTCHMED in multiple cancer types with MET aberrations, including non-small cell lung cancer, papillary renal cell carcinoma, and gastric cancer.

We're excited to see the global phase II trial, SAVANNAH, will report the top-line results next week at the European Lung Cancer Congress in Paris. The METex14 non-small cell lung cancer confirmatory phase IIIb trial also reached the positive result, and we received the full approval in the second line and also expanded the label to first-line indication. The updated OS results were also presented at ELCC next week.

China phase III randomized trial of savolitinib plus osimertinib versus chemo after progression on EGFR TKI also reached positive top-line results at the pre-planned interim analysis. We have submitted NDA and received the breakthrough therapy designation. The NDA is currently under priority review. The global SAMETA trial in PRCC also completed enrollment, and other trials led by AZ and China are also currently enrolling patients in lung cancer and gastric cancer. Next slide.

The SACHI China phase III trial met the primary endpoint of PFS at the interim analysis. We had the breakthrough designation, and then the NDA under priority review. SACHI evaluated the combination of savolitinib and TAGRISSO for the treatment patient with the EGFR mutant non-small cell lung cancer with MET amplification after progression of first, second, and third-generation TKI and compared with the chemotherapy chemo primary structure pemetrexed plus platinum doublet.

The results will be submitted for presentation at the upcoming scientific conference. Next slide. In October 2024, we announced positive results for SAVANNAH global phase II study demonstrated a high clinically meaningful and durable response rate. MET amplification or over-expression represents about 34% of TAGRISSO refractory patients. In the World Lung Cancer 2022, AZ reported 52% overall response rate, 7.2 months PFS, and 9.6 months duration of response in chemo naive patients.

Despite the MARIPOSA-2 and ORIENT-31, the second-line treatment remained very limited because SACHI and SAVANNAH data support the chemo-free option for biomarker-selected MET-positive EGFR mutant patients who progressed on the EGFR TKI. The combo has a very balanced safety, efficacy, and quality of life profile. Also, the global SAFFRON phase III trial will evaluate the efficacy and safety of this combo in MET overexpressed or amplified patients versus chemotherapy.

The recruitment is expected to complete this year. Next slide. Our next wave product, tazemetostat, is a global first-in-class EZH2 inhibitor and our first in-license product from Ipsen. Tazemetostat is approved in the US for certain epithelioid sarcoma and follicular lymphoma, and also in Japan for EZH2 gene-mutated positive follicular lymphoma. We have completed a China bridging study, and the results are consistent with the global study.

We are planning to report the top-line result later this year. The NDA is currently under review for third-line follicular lymphoma with EZH2 mutation, and we expect approval made this year. China is participating in the global phase III SYMPHONY trial, evaluating tazemetostat plus R squared in the second-line follicular lymphoma with a potential indication expansion. Next slide. We reported the first autoimmune agent, sovleplenib, is a highly differentiated oral SYK inhibitor.

It offers a dual mechanism targeting both B cells to prevent autoantibody production and also prevent macrophages destroying the platelet. This is an IQVIA report on the China ITP treatment landscape. We believe sovleplenib not only can compete in this quarter million ITP patients who are currently on alternative treatment, but also potentially help patients who lost follow-up, primarily due to no other alternative effective treatment. Next slide.

The phase III ESLIM-01 result, we reported the result last year at the European Hematology Association meeting, demonstrated a robust overall response rate of 71% and a durable response rate of 48% in relapsed refractory primary ITP patients. These high response rates are on par with almost all the other alternative treatments, and particularly in this patient with a highly pretreated patient, over 75% of the patients had prior treated with TPO/TPO-RA.

Updated results were also presented at the ASH meeting last year, showing a long-term treated treatment lead to a durable response rate of 51%, and also the overall response rate of 81%. Significantly better than many other treatment options. Next slide. The sovleplenib, I mentioned the NDA is currently under review, and we are working closely with NMPA and look forward to bringing this innovative medicine to the patients.

We have another indication, autoimmune disease in development, the warm antibody autoimmune hemolytic anemia. The phase II result was also presented at EHA last year and the subsequent publishing in Lancet Hematology. The sovleplenib demonstrated encouraging hemoglobin benefit compared with placebo, with an overall response rate of 43% versus 0% in the placebo group for the first eight weeks, and also the overall response rate of 67.7% and the durable response rate of 47.6% during the 24-week of sovleplenib treatment.

It also demonstrated a favorable safety profile. We initiated the phase III portion of the ESLIM-02 study in the warm antibody autoimmune hemolytic anemia, and we are currently enrolling patients and on track to finish enrollment this year. Next slide. Pancreatic cancer is a deadly disease with huge unmet need, with a five-year survival rate of less than 13%.

It is an immune cold tumor and usually does not respond to immunotherapy. Surufatinib, already marketed in neuroendocrine tumors, is a VEGF, FGFR, and CSF1R inhibitor and also shows immune modulating function. We are currently conducting a phase II and three trial of surufatinib in combination with camrelizumab and chemotherapy with treatment-naive pancreatic cancer. This study was informed by an investigator who initiated the trial, presented at ASCO GI last year, using surufatinib combined with camrelizumab, the Hengrui PD-1 inhibitor, plus chemotherapy in the front-line setting.

The overall response rate was 50% versus 27% in the chemo arm. The median PFS and OS reached nine months and 13 months, respectively, compared with only 5.8 months and 8.6 months in the control group. The phase II stage is already fully enrolled, and we are expecting to have the phase II readout later this year.

Next slide. Here, I'm going to update you about our antibody target therapy conjugate, the ATTC platform. For the past three years, we really initially invested a significant resource into this new platform, which should provide multiple drug candidates in the future. Compared with the traditional ADC, the toxin payload is replaced with the target small molecule.

This ADC has several key differentiations compared with the traditional ADC platform. It could have better efficacy through antibody small molecule combination that will target specific mutations. It can overcome drug resistance and potentially support combination with target therapy, with chemo, and immunotherapy, particularly in the early stage, early line of setting with the standard of care. On the safety side, it has improved the safety given with a lower on-target and off-tumor toxicity of small molecule.

It has less myelosuppression compared with chemo-based ADC, and usually we can think of a better quality of life than cytotoxin-based conjugate. It also has a tracted PK profile resulting from antibody-guided delivery to target sites will improve the bioavailability and reduce drug-drug interaction. Okay. Also, the ATTC platform has the potential to incorporate high molecular weight drugs payload, such as PROTACs or protein-protein inhibitors.

Okay. Next slide. Yeah, this slide, I'm going to show you a preclinical proof of concept of our target ATTC. In this case, our target antibody is linked to a target therapy payload, the TT1, with a special linker. On the left figure here, you can see the target antibody, which is shown in green here, and a small molecule payload, TT1, showing red, have a tumor growth inhibition. The combination of both actually has a more synergistic effect.

It is very importantly, a single dose of the target therapy, the ATTC, shows a robust anti-tumor activity when it is compared with either the antibody alone, payload alone, or a combination of the antibody and payload together. More importantly, on the right-hand side, we also show the small molecule TT1 payload alone, where a combination with the antibody actually was not tolerated very well. It showed a body weight reduction.

The ATTC dosing does not influence the body weight. It is a very important preclinical proof of concept of ATTC. It shows a single dose ATTC delivers 14 days of tumor regression and also the good tolerability. This really demonstrates the unique feature for this ATTC platform. Next slide. Our next ATTC generation technology leverages our expertise in target therapy and also small molecule inhibitor and also the payload chemistry.

The conjugate potentially has a key advantage over traditional ADCs. On the right-hand side, it targets protein required for cancer growth, has a synergistic combination effect with functional antibody, and also the ability to combine with IO, chemo, or target therapy as a standard of care, particularly in the front-line setting. It can overcome chemo resistance, which is delivered by the driver mutation.

The benefit for further optimizing this can also overcome the small molecule with a narrow therapeutic window. A reduction of on-target and off-tumor toxicity of the platform is designated to deliver high potent concentration of small molecule. It can be dosed long-term with improved safety window, and we also reduce systemic toxicity of small molecule. Okay. Our first ATTC will, as Dr. Su mentioned, we are conducting the IND enabling study, and it could potentially be our first global clinical study could be initiated later this year.

To recap our R&D progress, HUTCHMED has a deep and broad portfolio in oncology, hematology, and recently in autoimmune disease. Our R&D team and the global partners remain focused and executed well for the past year. We have multiple near-term NDA approvals and also late-stage development catalysts in the next year. In addition, our no-worry ATTC platform will also lead to multiple potentially first-in-class, globally competitive assets into the clinical development in the next few years. Next, I'll turn to Dr. Su.

Weiguo Su (Executive Director, CEO and Chief Scientific Officer)

Okay. Thank you, Mike. Just to sum it up, we think the most important milestone for us in 2024 is that we achieved profitability ahead of our schedule. Looking forward, we are quite excited about the growth prospects.

As you can see here in the near term, we expect the top-line and bottom-line growth to accelerate behind FRUZAQLA launches around the world. The new indications in China, such as EMC this year and potentially RCC next year sometime. For savolitinib, we believe the new indication behind the SAMETA study in China in second-line EGFR mutation positive MET amplified patients, once approved, should give a big boost since it's targeting a much bigger patient population.

Certainly, more importantly for savolitinib, we are hopeful that SAVANNAH and SAFFRON studies, if successful, will support registration globally and allow us to bring this important medicine to patients globally. In addition, new product launches, tazemetostat, sovleplenib, and our now pan-FGFR inhibitor HMPL-453, will add further to the growth.

Looking ahead, midterm, we plan to leverage our strong cash to explore acquisition of products or M&A opportunities in China to add further to our commercial portfolio. Longer term, of course, we believe ATTCs will deliver and will ensure our long-term growth. Thank you very much. David, back to you.

Operator (participant)

Thank you, Dr. Su. We will now proceed to the Q&A session. Everyone on the line, please make sure you put down your name and maybe your institute in your name. There are two methods to ask questions. You can press the raise hand button at the bottom of the screen, and we will call your name. Then you can ask the question directly, or you can type the question in the Q&A box also at the bottom of your screen.

The first question will be Goldman Sachs, Paul Choi, or I think your line will be unmuted now. You can go ahead and ask a question.

Hi, this is Khalil calling in for Paul. Thank you so much for taking our question. I guess a couple of quick ones from us. Apologies if you already mentioned this, but just curious about your phase III plans for savolitinib in combination with TAGRISSO ex-China. And then secondly, I know you mentioned M&A briefly there. How should we think about the types of assets you're looking at and the implications for your cash balance in 2025? Thank you so much.

Weiguo Su (Executive Director, CEO and Chief Scientific Officer)

Okay. Thank you for the question. With regard to the phase III savolitinib, I'll just ask Mike to provide any details. Mike?

Michael Shi (EVP, Head of R&D, and Chief Medical Officer)

Yeah. Globally, for savolitinib, we have this SAFRON trial, phase III program. It's the TAGRISSO plus savolitinib in EGFR-resistant patient population, actually TAGRISSO-resistant patient population with the MET amplification and overexpression. The phase III trial is ongoing very well. It has 20 countries participating, over 200 sites open for enrollment.

We anticipate AZ will finish recruitment this year. We're also, based on the SAFFRON and the SAVANNA data, we actually will be very interested to see if that will lead to the global potential registration. Yeah. Since it's a randomized trial, it has the potential to, if it is positive, it will support a global registration, including US, EU, and Japan also.

Weiguo Su (Executive Director, CEO and Chief Scientific Officer)

Yeah. Okay. Thanks, Mike. Yeah. With regard to your second question, M&A or product acquisition or in-licensing of products, I mean, it's really to leverage our strong cash position. We have over $800 million in cash now.

As you know, we announced we are in the process of divesting our non-core business that will add further to our cash balance. In terms of the type of products or acquisitions or M&A, it's all about adding products to our portfolio, but preferably products in the oncology immunology area where potentially with synergy with our pipeline. We will be exploring potential opportunities. Thank you.

Got it. Thank you so much. Congrats on the progress.

Thank you.

Operator (participant)

Thank you. The next question will be from Jefferies, Clara Dong. Clara, your line is now open.

Clara Dong (Biotechnology Equity Research Analyst)

Hi. Good morning. This is Clara for Kelly. Thanks for taking our question and congrats on the progress. Maybe can you probably talk about your strategy to integrate your ATTC programs into your portfolio, like what kind of development path or indication choice you might initially pursue as you are moving your first candidate into clinics.

Also, I think you mentioned a platform has potential to generate multiple programs. Could you talk about what are your key criteria to nominate those programs? You mentioned first global trial could be initiated this year. Are you looking to run the global trial with a partner or independently? Thank you.

Weiguo Su (Executive Director, CEO and Chief Scientific Officer)

Thank you very much, Clara. Obviously, we think these ATTCs have really big potential, obviously targeted therapies. The first few targets we are working on are targeting major signaling pathways. These are genetic alterations known to be driver alterations with incidence rates 30-40% or higher in all tumors.

There is a lot of evidence that patients or tumors with these kinds of genetic alterations tend to benefit less from chemotherapies or to IOs or to traditional toxin-based ADCs. With this inhibition of these genetic alterations, hopefully, it will allow these patients to benefit better from the treatments. In terms of initial development plan, I mean, you can think of initially late line as a single agent, potentially single-arm pivotal studies. In parallel, I think the ultimate goal is to move these products into front lines.

I think the major advantage of these ATTCs is that we do not expect overlapping toxicities with front-line chemo-based front-line therapies, including chemo-based ADCs. Hopefully, they can be combined with whatever front-line SOCs so we can move these to front lines to target a much bigger patient population. Obviously, ultimately, it will all be clinical data that will guide us where to go. Hopefully, if proven in clinics, I think we believe they have huge potentials. Thank you.

Clara Dong (Biotechnology Equity Research Analyst)

Thank you.

Operator (participant)

Thank you very much. Our next question is from Bank of America, Alec Stranahan. Alec, your line is now open. Go ahead.

Alec Stranahan (Biotechnology Equity Research Analyst)

Okay. Great. Thanks, guys, for taking our questions and congrats on the progress last year. I guess two questions from us. First, when you look at the EU opportunity for fruquintinib, I guess, how do you see this adding to the top line over the course of 2025? Could this support or maybe even accelerate the already strong growth ex China, or is it maybe more of an incremental opportunity? Secondly, on Savo, what sort of incremental info from SAVANNAH should we expect next week at ELCC?

As a follow-up to that, what would you want to see in SAFRON for you and ASHRA to feel confident to proceed to global submissions? Is it essentially just confirming what we've seen in SAVANNAH, or are you maybe hoping for something more there? Thank you.

Weiguo Su (Executive Director, CEO and Chief Scientific Officer)

Yeah. Alec, thanks for the questions. For quintenib, it is obviously very early in global launches. Last year is mainly US, while approved by EU, by EMA, but it takes time to gain access. Really towards the very end of the year, it was launched in Spain. There are many more countries to go. I'm sure our partner, Takeda, is highly focused on EU. Also, Japan finally gained access in Japan and launched in Japan around Thanksgiving time. A lot to go in Japan as well.

I think all these markets will certainly accelerate the growth, same in the US as well. I think we think Takeda will do a great job as they've been very strong in the launches. Savolitinib, in terms of SAVANNAH and SAFFRON, SAVANNAH is a single-arm study. It will only support conditional approvals in the US and maybe a few other small countries that support this kind of system.

It is SAFFRON ultimately will support full approval around the world. SAFFRON obviously is the most important study. Yeah, it's enrolling very well, as Mike pointed out, and indicating a strong medical need with targeted therapies in this patient population. We are quite hopeful that SAFFRON study will complete enrollment very soon, and we can ultimately support the global registration. Thank you.

Alec Stranahan (Biotechnology Equity Research Analyst)

Thank you.

Operator (participant)

Thank you very much. Next question goes to Panmure Gordon, Julie Simmonds. Julie, I think your line is now open. Go ahead with your question.

Julie Simmonds (Equity Analyst)

Thank you very much. Yes, just following on fruquintinib, just wondering as far as sort of you're now looking at additional indications in China and getting some data on those, wondering how that potentially could get into global markets and what's required there.

Weiguo Su (Executive Director, CEO and Chief Scientific Officer)

Yeah. I mean, obviously, IO and VEGFR TKI combo has proven synergistic, the successful trial with fruquintinib and sintilimab combination in second-line endometrial cancer and now in a randomized study in renal cell carcinoma clearly confirms the synergy. In terms of outside China, obviously, we share all the data with Takeda, and this is clearly low-risk and proven clinical activity.

I think the only challenge is that sintilimab is not approved outside China. Whether we can replace sintilimab with a different PD-1 or other IO, it just makes it a bit more challenging. Clearly, PD-1 and VEGFR combo is a proven mechanism that will result in synergy.

Julie Simmonds (Equity Analyst)

Yeah. Excellent. Thank you. Just wondering back on the M&A side of things, what sort of stage of programs would you be looking at? Is this wanting to add to the later stage pipeline or back at the sort of early part of what you're doing?

Weiguo Su (Executive Director, CEO and Chief Scientific Officer)

I think it will be open-minded, but certainly preferably a late stage, something that could really immediately accretive adding to our commercial portfolio.

Julie Simmonds (Equity Analyst)

Lovely. Thank you.

Weiguo Su (Executive Director, CEO and Chief Scientific Officer)

Thank you.

Operator (participant)

Thank you. Next question goes to Cavendish, Adam McCarter. Adam, your line is now open. Go ahead.

Adam McCarter (Equity Research Analyst)

Thanks very much. Thanks for taking my questions, and congratulations on the results. My first question really is just on savolitinib again. Last month, during AZ's earnings call, we heard AZ executives say that what they're hearing based on the MARIPOSA study data is that utilization of J&J's drugs is likely to be most impactful in the second line in non-small cell lung cancer.

Based on this, I'm just interested to hear what management view is on how they see the MARIPOSA trial potentially affecting savolitinib's positioning because it does feel there's going to be an impact there. Second question is on FRUZAQLA. I see from the announcement that FRUZAQLA sells primarily in the fourth line with growth potential into third line. Do you have a feel on the levels of market penetration that can be achieved for FRUZAQLA in the US?

Based on the sales, it seems that you've taken quite a big significant contribution to the market already. Just interested to how much more headroom is there in there for you to go at? My final question is just on R&D expenses. Obviously, those were down quite a bit over the period. Just wondering how we should think about the outlook on future R&D expenditure, particularly with the level of investment you're going to be putting into the ATTCs and perhaps just overall sort of OpEx in general. Thanks very much.

Weiguo Su (Executive Director, CEO and Chief Scientific Officer)

Okay. Thanks for the questions. I'll give you a quick answer on FRUZAQLA, and then I will ask Mike to answer your question on Savo and also the R&D expenses or budget. FRUZAQLA, yes, in EU, Japan, it's all fourth-line indication or label. Clearly, initially, it will be fourth line.

In the United States, the label is third line and above. Obviously, fourth line is blank right before the approval. So it's the low hanging fruit there. I'm pretty sure the label covers the third line. I'm pretty confident our partner, Takeda, will try their best to penetrate the third line. Really, it's a very different therapy with proven efficacy and safety without the chemo, without myelosuppression. Certainly, particularly for elderly patients or the immune-compromised patients, myelosuppression could be a problem. Savo and R&D, I'll leave it to Mike.

Michael Shi (EVP, Head of R&D, and Chief Medical Officer)

Yeah. Thank you, Adam. Yeah. In terms of competition, right, I mentioned the MARIPOSA is really in the unselected patient population, and also it's a chemo combo, right? You're going to see not only the traditional chemo-based toxicity, myelosuppression, the hematology toxicity, but also there are some very challenging toxicity for skin toxicity.

The big disadvantage is really the dosing, right? They have to do the split dosing and very frequent infusion. It really presents a, certainly, it's approved, but it's not a very clear biomarker-selected patient population. For savolitinib and TAGRISSO combination, it's really a very convenient oral regimen and also has a very precision-selected target patient population.

I think just for the SACHI, for the SAVANNAH data, you're going to hear next week, SACHI in the future is MET amplified overexpressed patient, is really representing a big group of patients, 34% of patients with MET overexpression amplification have a larger patient population with a clear driver mutation. This target therapy is really being effective, very convenient. We believe if it is, I mean, if it is approved or has an alternative, it certainly has a convenient and the precision medicine-based approach.

I think just by looking at its therapy, this is a really high M&E and with a convenient dosing. We think even I think AZ is also thinking this is really the competitive advantage for the oral target therapy combination. R&D expense, right? We are actually very excited about our ATTC platform, right? This is truly the first-in-class.

We think all these assets are very globally competitive assets. I think the strength also for our platform is we are very carefully selected the antibody. Dr. Su alluded to these potentially very broad tumor type, higher percentage of the driver to mutation with a lot of commercial opportunity down the road. Certainly, we do want to take these assets as our priority to invest.

My envision is really initially we're going to do a rapid global dose escalation, really have as a late-line expansion clinical proof concept. Once we demonstrate clinical activity, we can still leverage a lot of opportunity. Not necessarily everything has to be done by ourselves, right? Certainly, we have multiple assets by this platform. We can pretty much duplicate and repeat the process.

Hopefully, when the clinical proof concept is demonstrated, we can bring potential party in. Not necessarily just really exponentially grow our R&D budget, but through potential BDR opportunity, we can manage the expense. Certainly, these are potentially exciting competitive molecule assets. We certainly will be a priority for company to invest for the future growth. Yeah.

Weiguo Su (Executive Director, CEO and Chief Scientific Officer)

Okay. Thanks, Mike.

Adam McCarter (Equity Research Analyst)

Thanks very much again, and congratulations.

Michael Shi (EVP, Head of R&D, and Chief Medical Officer)

Thank you.

Operator (participant)

The next question goes to UBS, Chen Chen. Chen Chen, your question, your line is now open. Go ahead with your question. Thank you.

Chen Chen (Equity Research Analyst)

It's very great to see the encouraging preliminary data of your ATTC. I'm just wondering how many ATTC candidates can move to clinical stage this year. Are you just focusing on one key candidate, or will you focus on a few ATTC candidates?

Weiguo Su (Executive Director, CEO and Chief Scientific Officer)

Yeah, the short answer is multiple, as you heard from Mike, right? We have already multiple payloads targeting different genetic drivers, but every payload has the potential to be linked to different antibodies based on the tumor antigen expression levels in various different tumors. It's all about delivering these highly potent targeted therapies to different tumors.

There will be multiple. This is the year that it will get started. Maybe R&D filings, maybe one or two, maybe two this year, depending on timing and how the preclinical R&D enabling talks progress. Certainly, one could be two, but there will be more to follow later next year or even beyond.

Chen Chen (Equity Research Analyst)

I see. That's quite clear. My second question is very quick. Previously, you guided break-even in 2025, and it's very exciting that you have already achieved this in 2024. I just want to double-check your break-even target in 2025. Is this still the guidance now?

Weiguo Su (Executive Director, CEO and Chief Scientific Officer)

The short answer is yes. Maybe Johnny can provide more color on this. Certainly, we think we'll be profitable from here on. We believe we reached a self-sustaining kind of mode of operation. Yeah.

Johnny Cheng (Executive Director, CEO, and CFO)

Yes. Thank you, Dr. Su. So, Chen Chen, we have only been giving out this revenue guidance for our oncology business. I think in terms of our target, as Dr. Su mentioned, we have in advance achieved our self-reliance, self-sustaining profitability model already in 2024.

In fact, we made profit 2023 thanks to the upfront income that we recognized from Takeda. This year, from our ongoing business, we have been able to make break-even and site profit this year. Going forward, as we said, we will maintain this goal, and we will continue to have this pathway. This is not our guidance strictly to the market. One can take because of the divestment of our non-core business, we will be recognizing a substantial high amount of profit in 2025.

Chen Chen (Equity Research Analyst)

That's great. Thank you.

Johnny Cheng (Executive Director, CEO, and CFO)

Thank you.

Operator (participant)

Thank you. We have one question on the line. This is from Morgan Stanley, Jack Lin. This is questions regarding our ATTC platform. Question one is, is there any molecular difference or modification in the TKI being used in the payload of our ATTC as compared to the traditional TKI being consumed orally?

That's question one. Question two is, would it be possible to use more potent payload similar to how ADC technology has allowed to use more toxic payload that would normally not be able to use systematically? That's question number two. The final question is, what do we think about the future potential dosage or dosing frequency of our ATTC drug candidate?

Weiguo Su (Executive Director, CEO and Chief Scientific Officer)

Okay. Thanks. It's a lot of questions here. Certainly, structure of the TKIs, these are all novel structures, chemical structures will be protected by patents. They will obviously differ from whatever is available out there. I actually don't even think anything approved against these targets. In terms of toxicity or very potent TKIs, I mean, that's the whole idea, right?

Johnny Cheng (Executive Director, CEO, and CFO)

The ATTC, we hope to improve clinical activity through combination between the antibody and the payload, at the same time reducing toxicity because the free circulating small molecule payload will be extremely low. Any toxicity associated with the payload will hopefully be much reduced. I think that's the key rationale behind ATTCs.

Certainly, as Mike already explained in detail, the clear definition from traditional toxin-based ADCs are that these ATTCs, they are targeted therapies. They are much less, we expect much less myelosuppression or overlapping toxicities with the chemos, and hence can be combined, hopefully, much better with frontline chemo-based standard of care. Really, the big potential is in combination.

Thank you, Dr. Su. Maybe we'll have the very final question of the night, HSBC, Cindy Chai. Cindy, your line is now open. Please ask your question.

Cindy Chai (Equity Research Analyst)

Hey, thanks for taking my questions and congrats to the achievement. I just have a quick question. We know that there are US tariffs here. I just wonder, as fruquintinib is still produced by HUTCHMED, what's the tariff's impact in the future? Also, what's the progress of our manufacturing transfer to Takeda and whether they will, and after the manufacturing transfer is finished, whether they will produce fruquintinib in the US or in Japan? Thanks so much.

Weiguo Su (Executive Director, CEO and Chief Scientific Officer)

Okay. Thank you for the question. Obviously, tariffs on pharmaceutical products are being proposed by President Trump, but no details at the moment in terms of a level. As you all know, the cost of goods or cost of manufacturing for all pharmaceutical products is always relatively low. The impact to our products, let's say FRUZAQLA, remains to be assessed. At the moment, it's really not clear.

Johnny Cheng (Executive Director, CEO, and CFO)

In terms of tech transfer to Takeda, it's going very well. Both API and drug product ultimately can be sourced outside China. China can remain as a supplier, HUTCHMED can remain as a supplier, but at least there will be multiple sources to support global market. Thank you.

Operator (participant)

Thank you, everyone. I think we'll wrap it up here. Thank you for all the questions. Dr. Su, would you have one last remark?

Weiguo Su (Executive Director, CEO and Chief Scientific Officer)

Yeah, absolutely. I just want to thank everyone for participating in this call. As we presented here, HUTCHMED is in a very good position. We have very strong cash. We have multiple products this year going through regulatory reviews and hopefully come out positive. We have FRUZAQLA going well and expected to continue the momentum and SAVANNAH or SAFFRON.

Ultimately, hopefully, we are hopeful that we can bring this important medicine to patients globally. All these will ensure accelerated growth for us for years to come. Of course, longer term, yeah, it's all about next wave of innovation, particularly ATTCs. Thank you all for participating in the call and look forward to interacting with you.

Operator (participant)

Thank you, everyone. We'll now end the call.