Zai Lab Limited

Hello, ladies and gentlemen. Thank you for standing by, and welcome to Xylep's second quarter 2025 financial results conference call. At this time, all participants are in the listen-only mode. Later, we will conduct a question and answer session, and instructions will follow at that time. As a reminder, today's call is being recorded. It is now my pleasure to turn the floor over to Christine Cho, Senior Vice President of Investor Relations. Please go ahead, ma'am.

Thank you, operator. Hello and welcome, everyone. Today's earnings call will be led by Dr. Samantha Du, Xilab's founder, CEO, and chairperson. She will be joined by Josh Smiley, President and Chief Operating Officer, Dr. Rafael Amado, President and Head of Global Research and Development, and Dr. Yajing Chen, Chief Financial Officer. Jonathan Wang, our Chief Business Officer, will also be available to answer questions during the Q&A portion of the call. As a reminder, during today's call, we will be making certain forward-looking statements based on our current expectations. These statements are subject to numerous risks and uncertainties that may cause actual results to differ materially from what we expect due to a variety of factors, including those discussed in our SEC filings. We will also refer to adjusted loss from operations, which is a non-GAAP financial measure. please refer to our earnings release furnished with the SEC on August 7, 2025, for additional information on this non-GAAP financial measure. At this time, it is my pleasure to turn the call over to Dr. Samantha Du.

Thank you, Christine. Good morning and good evening, everyone. Thank you for joining us today. As we reach the midpoint of 2025, satellite is entering a pivotal phase. killing our commercial business, advancing our global pipeline, and executing on the goals we outlined at the beginning of the year. Our long-term vision of becoming a leading global biopharma remains strong, grounded on consistent execution and meaningful progress across the business. We are reaffirming our full year revenue guidance of $560 million to $590 million USD. We remain on track to achieve profitability in the fourth quarter, a milestone made possible by the efficient, scalable model we have built over the years. In our original business, momentum is building as we head into a period of significant growth supported by multiple new term launches. This includes pipelining the product opportunities like ZipGuard in multiple autoimmunocations and povitacacept, a dual-bath APOE inhibitor with broad potential. We also anticipate approvals for CARX-T in schizophrenia and Tdac in cervical cancer, both currently under regulatory reviews in China. We're preparing for submissions for other later stage assets, including bimethylamine for cancer and tumor treatment fields for pancreatic cancer. Combined with our broader regional pipeline, these programs position us well for long-term growth. On the global R&D front, we're advancing a pipeline of innovative, globally competitive programs. GL1310, our DL3 ADC, continues to demonstrate first-in-class and best-in-class potential in small cell lung cancer, as illustrated by the updated data presented at ESCO. We also see encouraging early signals in other difficult-to-treat tumors, such as neuroendocrine carcinomas. Beyond that, we're advancing our next wave of innovative global programs into the clinics, including GL1503, a bi-specific R13R31 study for atopic dermatitis, and GL6201, our RRC15-ADC for solid tumors, This development continues to be a core pillar of our growth strategy. As global interest in China-originated innovation rises, Zalas is uniquely positioned to act as a bridge between China's thriving bio-ecosystem and global markets. Our deep local know-how and global R&D expertise allow us to source and develop high potential assets emerging from China and the rest of the world, while continuing to expand our internally discovered global pipeline. We're also leveraging AI across the organization. For example, optimizing clinical trials, accelerating timelines, and sharpening our commercial analytics. These ongoing efforts are already improving our speed precision, and efficiency. Going forward, we will apply more AI tools to accelerate our future growth. We remain disciplined in our operations, scaling efficiently while investing strategically in both commercial execution and pipeline innovation. The progress we have made this quarter reinforces our conviction. Jean Wood's satellite is becoming a profitable, high-growth company with global impact, powered by innovation, disciplined execution, and a deep commitment to delivering long-term values for patients and shareholders alike. Now I turn the call over to Josh. Josh?

Thank you, Samantha, and hello, everyone. Let me start with VivGuard, where strong commercial execution continues to drive momentum in GMG. In the second quarter, we saw record levels of patient utilization supported by a steady flow of new patient starts and increasing treatment duration. We are seeing a meaningful shift toward maintenance use, a reflection of growing physician confidence in VivGuard's long-term benefits. These positive trends are supported by ongoing physician education and patient support programs aimed at extending treatment duration. We expect this momentum to further accelerate following the July update to China's national GMG guidelines, which meaningfully elevate DivGuard's positioning. The new guidelines recognize minimal symptom expression, or MSE, as the primary treatment goal in GMG and highlight DivGuard's ability to achieve MSE rapidly and durably. DivGuard has the highest MSE rates ranging from 40 to 73% across clinical studies and stands out for its rapid onset and deep and sustained efficacy. VivGuard is now recommended for early use in mild to moderate and highly active patients and for sustained long-term treatment to maximize benefit, marking a major step forward for biological adoption for treating GMG in China. We see significant long-term potential for VivGuard. Physicians are initiating treatment earlier and shifting away from steroids, yet VivGuard penetration in GMG is only 10%. We are well-positioned to drive broader adoption and to capture the substantial opportunity that lies ahead. Once listed on NRDL, we believe that subcutaneous formulation will further accelerate uptake by driving deeper market penetration and expanding patient access. The launch in CIDP is also underway, with efforts focused on increasing supplemental health insurance coverage and driving awareness. Our planned submission of the pre-filled syringe remains on track and will further differentiate the brand through added convenience and improved adherence. Beyond GMG and CIDP, we are actively pursuing label expansion opportunities across a range of immunology indications with significant unmet need, including seronegative GMG, ocular MG, myositis, lupus nephritis, and sogrance. Taken together, these efforts reinforce our view that DivGuard can exceed $1 billion in peak sales and become a foundational immunology brand in China. Turning to the broader commercial portfolio. Zajula had a softer quarter due to evolving competitive dynamics within the PARP class. That said, we are already seeing signs of stabilization entering the second half of the year. We anticipate continued volume expansion across the PARP class and expect Zajula's sales to strengthen in first-line ovarian cancer, where it maintains a differentiated safety and efficacy profile supported by strong China patients' data and first-to-market advantage. We are confident in Zajula's return to growth later this year. Zactoro continues to see robust demand and highly positive feedback from physicians treating crab infections, a serious and underserved public health threat in China, with approximately 300,000 Acinobacter cases annually. As we work to localize manufacturing, supply constraints may modestly limit near-term growth in 2025, but underlying demand remains strong. With Octairo, we are taking a focused, efficient approach to commercialization. While near-term revenue is expected to be limited, we believe its best-in-class clinical profile in ROS1-positive non-small-cell lung cancer, including strong CNS activity and durability in both TKI-naive and pretreated patients, positions Ogtiro as an important treatment option for patients. We will continue to pursue efficient ways to broaden our reach to realize the full value of its long-term potential. Turning to our financial position, we continue to execute against our profitability plan, maintaining disciplined spending while investing in growth. For the second quarter of 2025, operating loss improved by 28% to $54.9 million. On an adjusted basis, which excludes certain non-cash expenses, operating loss was reduced by 37% to $34.2 million, keeping us firmly on track to reach profitability on an adjusted basis in the fourth quarter. We also expect a strong set of near-term regulatory milestones ahead. CAR XT and TIVDAC are under review by the NMPA, and we plan to submit applications for Vivgard's pre-filled syringe for GMG and CIDP, Femurituzumab for gastric cancer, and TT fields for pancreatic cancer in the coming months. To support these potential near-term launches, we are leveraging a scalable, resource-efficient commercial model. repurposing teams where possible, and targeting field force deployment in high-impact areas. For example, our Zajula team will support TIVDAC, our Kinloch team will lead efforts for bemerituzumab, and we plan to cover 85% of the schizophrenia market with a highly focused team of approximately 150 representatives for CAR-XT. At the same time, we are advancing several operational efficiencies, including scaling support for VivGuard, localizing manufacturing for key products, and improving cost leverage across the portfolio, all of which will drive both strong top-line growth and margin expansion. Business development remains a strategic priority. We are focused on three core areas, strengthening our global pipeline with externally sourced innovation, expanding our China portfolio with best-in-class assets, and pursuing outlicensing and global partnerships to unlock the full value of our pipeline on the global stage. With continued commercial momentum, an innovative and advancing pipeline, and a path to profitability, we are confident in our ability to deliver meaningful long-term growth and value. And with that, I will now pass the call over to Rafael to discuss the great progress within our pipeline.

Thank you, Josh. I'll start with highlights from our global pipeline since our last earnings call, and then cover upcoming milestones. Let's start with ZL1310, or Socioelectric Politican, or ZOZI for short. Our first-in-class ELL3 targeting ADC for small cell lung cancer and other neuroendocrine tumors. At ASCO this year, we presented those finding results in patients with previously treated extensive stage small cell lung cancer. Across all those levels in the second line setting, the unconfirmed response rate was 67%, and the disease control rate was 97%. The most promising combination of response and tolerability was observed at 1.6 milligrams per kilogram, which showed a 79% unconfirmed overall response rate and 100% control rate of the disease, which is among the strongest efficacy response signals seen in this setting to date. At a median follow-up of 3.4 months, median duration of response had not yet been reached and 29 of 38 responders remain on study. Importantly, we observed compelling intracranial activity, an important and met need in small cell lung cancer, where up to 70% of patients developed breaking metastases. Among these patients, the ORR was 68%, and it was 86% in patients without prior cranial irradiation. Again, the highest intracranial response was reported. SOSI also demonstrated a well-tolerated and differentiated safety profile. At target doses below 2 milligrams per kilogram, there were no grade 2 or higher interstitial lung disease cases, and grade 3 and above treatment-related adverse events occur in just 6% of patients with no drug-related discontinuation. This data supports the potential of SOSI as a clinically meaningful treatment for patients in second line small cell lung cancer and other lines of therapy, either as monotherapy or in combination. We're pleased to receive a fast track designation from the FDA in small cell lung cancer, adding to the orphan drug designation granted earlier this year, and are pursuing breakthrough therapy designation. We have aligned with the FDA on the accelerated approval pathway and are finalizing details on the pivotal study design in second-line small cell lung cancer. We remain on track to initiate the registration of study later this year. Given its favorable safety profile at 1.6 milligrams per kilogram, SOSI is also well-suited for use in the frontline setting. We are rapidly enrolling patients in the combination dose escalation portion of the study, which will be followed by dose optimization and then a pivotal computation trial after the defined follow-up period. We expect to provide a clinical trial update of CERSI in combination with a tesolizumab in the next year. Beyond small cell lung cancer, SOSI is also being studied in other neuroendocrine carcinomas where enrollment is ongoing in a global phase 1-2 study, which may have registration potential pending regulatory discussions. We plan to present preliminary data at a medical conference in the first half of the next year. Moving to CL1503, our internally developed IL-13 and IL-31 by specific antibody for atopic dermatitis. In June, we presented preclinical data showing durable dual inhibition of both itch and inflammation pathways. While IL-4, IL-13 inhibitors have markedly improved outcomes in atopic dermatitis, symptoms mediated by IL-31 often remain only partially alleviated, contributing to limited and incomplete clinical responses to currently available medications for many patients. GL1503 dual mechanism and extended half-life may enable less frequent dosing and more comprehensive disease control. We are on track to initiate a phase one study for moderate to severe atopic dermatitis later this year with both IV and subcutaneous formulations progressing as planned. Importantly, 1503 exhibits immunomodulatory properties that are extending beyond atopic dermatitis. with potential applications across a range of interleukin-driven diseases, laying the foundation for a pipeline of future indications. More broadly, across our global portfolio, we're advancing our internal discovery efforts in parallel. We are actively pursuing external opportunities to expand our pipeline with early-stage compounds from China and beyond. Now turning to our regional programs, let's start with oncology. The maritouzouma, a first-in-class FGFR2B targeting therapy for gastric cancer. In June, we announced positive top-line results from the Global Phase III 42-101 study in first-line FGFR2B positive gastric, gastroesophageal junction cancer. The marituzumab plus chemotherapy demonstrated a statistically significant and clinically meaningful improvement in overall survival as compared to placebo plus chemotherapy in patients with unreceptible, locally advanced, or metastatic gastric or gastroesophageal junction cancer with FGFR2B overexpression and who are non-HER2 positive. FGFR2B overexpression was defined as 2 plus or 3 plus staining greater than 10% of tumor cells by centrally performed immunohistochemistry. The most common treatment effects adverse events in patients treated with Vemurituzumab plus chemotherapy were reduced visual acuity, keratitis, anemia, neutropenia, nausea, corneal epithelium defect, and dry eye. While ocular events were consistent with the Phase II experience and observed in both arms, they occurred with greater frequency and severity in the Phase III Vemurituzumab arm. This data, which our partner Amgen plans to present at an upcoming medical meeting, support a regulatory submission in China. Meanwhile, we look forward to the top-line results from our second global phase 3 study, Fortitude 102, a phase 1B3 study of a marituzumab plus chemotherapy and nivolumab in patients with first-line gastric cancer. This data readout is anticipated in the second half of 2025 for the first half of 2026. In pancreatic cancer, our partner NovoCure announced positive results from the Phase III Panova III trial evaluating tumor-treating fields with chemotherapy in newly diagnosed patients with unresectable, locally advanced pancreatic adenocarcinoma. The study met its primary endpoint of overall survival, representing the first Phase III study success in this setting. We believe this therapy could meaningfully expand treatment options for patients with limited alternatives in pancreatic cancer, and we expect to submit in China this year. Now moving to our key late-stage regional programs in immunology. For FKTG-MOV, we continue to explore its potential to treat other IgG-mediated autoimmune indications, including thyroid eye disease, or TAD, myositis, seronegative GMG, ocular NG, Sjogren's disease, and lupus nephritis. In the second half of this year, we expect top-line results from the Global Phase III Study of seronegative GMG and the Phase II Study of lupus nephritis. In addition, we will join the Registrational Unity Study of epiphytic mugs subcutaneously administered by pre-filled syringe in Sjogren's disease in Greater China in the third quarter of this year. Covitacizep is a dual antagonist of the BAFTA and APRIL pathway. China has already joined the Global Phase III Reniers trial in IgA nephropathy, and enrollment of the interim analysis cohort is now completed. Our partner, Vertex, will conduct an interim analysis once this cohort reaches 36 weeks of treatment, with the potential to file for accelerated approval in the U.S. in the first half of 2026. We also plan to join the Global Pivotal Phase 2-3 study in primary membranous nephropathy expected to start in the second half of this year. Moving to VRDN003, an anti-IGF-1R antibody, a potentially best-in-class therapy in thyroid eye disease. It has the same binding domain as Beligrichag, and it is administered subcutaneously. Maligretag has consistently demonstrated reductions in proptosis, diplopia, and clinical activity score across both active and chronic thyroid eye disease in Phase III studies. The infrequent dosing regimen of every four weeks or every eight weeks presents significant potential as a transformative option for patients with TADS. The two global registrations of Reveal 1 and Reveal 2 studies are enrolling and our partner Viridian is expected to provide top-line results in the first half of 2026. We are working on initiating Phase I PK study in China and a Phase III registrational study in TED upon CDE agreement expected in the fourth quarter of 2025. These updates underscore our continued focus on pipeline renewal as well as discovery and development innovation and execution across oncology and immunology. I look forward to sharing further progress updates in the coming quarters. And now Yajing will give an overview of our financial results. Yajing?

Thank you, Rafael. Now I will discuss highlights from our second quarter 2025 financial results compared to the prior year period. Total revenue grew 9% year-over-year to $110 million in the second quarter. primarily driven by higher sales of VidGuard supported by duration of therapy extension and increasing market penetration, as well as that DORA, which was launched since the fourth quarter of 2024. Our focus on financial discipline and efficiency efforts was also reflected on the expenses side. R&D and SG&A as a percentage of revenue declined significantly year over year. R&D expenses for the second quarter decreased 18% year-over-year, mainly due to decreased personnel cost and the clinical trial cost as a result of resource prioritization and the efficiency effort. HG&A expenses for the second quarter decreased 11% year-over-year, mainly due to the strategic resource allocation and the efficiency improvement. As a result of operating leverage we're building into our business, our large fund operations decreased 28% for the second quarter to $54.9 million. When you adjust our large fund operations to exclude certain non-cash items, specifically depreciation, amortization, and share-based compensation, we had adjusted large fund operations of $34.2 million in the second quarter. reflecting year-over-year improvement of 37 percent. Based on our operating plan and our anticipated revenue growth, we expect to achieve profitability on the adjusted basis by the fourth quarter of this year. Looking ahead, we expect to deliver quarter-over-quarter total revenue growth in 2025 with a meaningful acceleration anticipated in the later part of the year. We remain confident in reaffirming our four-year 2025 total revenue guidance of $560 million to $590 million. This revenue forecast reflects strong growth for BizGuard franchise, continued growth for our base business, and contributions from newly launched products. We are in a strong financial position, ending the quarter with a cash position of $832.3 million. And with that, I would now like to turn the call back over to the operator to open up a line for questions. Operator.

Thank you. We will now open the line for questions. To ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. Please stand by while we compile the Q&A roster. We will now take our first question from the line of Jonathan Chang from Liver Inc. Partners. Please go ahead, Jonathan.

Hi, guys. Thanks for taking the questions. First question, congrats on the positive Fortitude 101 study results. Can you help us understand the potential opportunity for BEMA in frontline gastric cancer? What biomarker status and FGFR2B threshold would patients need for treatment with BEMA? And can help us characterize the safety profile observed in the one on one study.

Morning, Jonathan, it's Josh. Thanks for the message. I'll start on commercial and then turn it over to Rafael to talk a little bit more about the profile at first. There's over 450,000 patients with gastric cancer in China. about a third of whom over expressed FGFR2B, so very significant patient population. I think given what we know of the clinical benefits of this product and potential treatment duration, we're, you know, quite excited and confident that there's over time a billion-dollar sales potential opportunity in this potential indication. We're already in this space with Kinloch. We've got about 100 sales reps who promote Kinloch today. We'll use that sales force and build on it to take advantage of the opportunity here. And again, we're quite excited by this product. It's going to deliver significant benefits to a very big patient population in China. And I'll ask Rafael to make some more comments.

Yeah, thanks, Josh. And thanks for the question. As I said in the prepared remarks, this is a drug for patients with overexpression of FGFR2B. And that's about a third of patients, 30% or so. The cutoff is 2 plus to 3 plus, at least 10% of the cells. So in terms of patient numbers, it's close to 140,000, 150,000 new cases in China per year, which is very sizable, and we are preparing to launch this product with diagnostic as well. In terms of the toxicity, as I mentioned, the key toxicity was mild suppression, which is probably more related to chemotherapy, and then ocular toxicity, which was expected, and it was seen in the phase two study, the fight trial. So, toxicity greater than 25% included mostly corneal toxicity that affected visual acuity. So, either punctic keratitis or epithelial defects as well as dry eyes. And we saw this actually in the placebo arm as well. But it's more pronounced in the treatment arm and more common in the 101 study than it was seen in the phase 2 study. And that may be because we included a more comprehensive and standardized ocular monitoring in that trial. And this is expected, as I said, the receptor is expressed in epithelial cells in the cornea. It can be monitored by ocular consultation. Patients can be prophylaxed. It happens well into the treatment, so it doesn't happen right away. And at least in the phase two study, they were reversible. So the details of all the safety will be presented at an upcoming meeting that Amgen has guided towards. And then in terms of, you know, how this will play out with regards to benefit risk, well, you know, it depends on the benefit that you will see when the presentation comes up. But these are patients that have a particularly poor prognosis, and there is a meaningful treatment effect that, you know, needs to be taken into account. with this very aggressive form of cancer that has very limited treatment options.

Understood. And maybe second question, if I may. Can you discuss your confidence levels in achieving your 2025 revenue guidance and profitability goal by year end? And how should we think about the contribution of VivGuard in achieving these goals? Thank you.

Thanks, Jonathan. It's Josh. First, we reaffirmed our top line guidance of $560 million to $590 million in sales. So obviously we're confident in that range. And on profitability, we also have reconfirmed that we see us achieving profitability on a non-cap basis in Q4. So I think full speed ahead on both of those. As it relates to the sales We do expect accelerating growth in the second half of this year, driven certainly by VivGuard as one of the big drivers here. We're pleased with our performance in the second quarter. Saw, you know, record patient numbers in terms of patient starts, and we're seeing, you know, every month we're seeing an increase in patient duration or numbers of doses or cycles per patient. We expect that to accelerate in the second half of the year. both as we continue to build experience with physicians and patients, but also leveraging the new national guidelines for GMG that were issued in July. So, you know, you should expect to see the kind of quarter-over-quarter acceleration or growth in sales for VivGuard that we saw in the second quarter, and again, we're quite happy with those trends. Sejula, we expect growth in the second half of the year. We did see some declines in the second quarter, but I would say that's mostly related to the choppiness and disruption that comes with a major competitor going off patent, that's Limparsa. and new competitors coming on, but we're quite confident in our position with DeJewel as the market leader in first-line ovarian cancer. And again, we are already seeing good recovery in the third quarter, so we'd expect to see sales growth there. So again, confident about the trajectory and the shape of the growth for the second half of the year. With that growth then, if you look at our overall operating expenses, that growth drives us towards profitability. And, you know, if you look historically quarter over quarter, we continue to see good improvement each quarter and have good confidence that we'll get there in the fourth quarter of this year. So thanks.

Thanks for taking the questions.

Thank you. Our next question comes from the line of Anupam Rama from JP Morgan. Please go ahead, sir.

Hey, guys. Thanks so much for taking the question. You talked about the second half growth levers with this guard, and you talked about the stabilization of Zajula looking to the second half. But just wondering if there's any outsized growth expected from the broader commercial franchise in terms of New Zyra or Xduro that might contribute meaningfully to getting to guidance and profitability by the end of the year.

Thanks, Anna Palm. It's Josh. Yeah, I think first, if you look at Zactoro and Augtyro, both products are in the beginnings of the launch phases. We're really excited about the potential of both products. I think with Zactoro, you should expect to see continued good growth, as we mentioned in the beginning of the the call. I think the demand is strong. We're still working through supply and making sure we can fill as much of that demand as possible. So the more product we can get into the country, the better off we'll be. And we should expect to see continued good growth there. Somewhat limited, I think, in the second half of the year by supply constraints. But I think long-term for this product, we're quite excited. I think with Ontario, we're taking a focused approach to to the launch here, but also would expect to see good growth in the second half of the year. We have good pricing on NRDL and Of course, this is a product for patients with a mutation that provides really significant benefit. So, yeah, so I think as you, you know, look at your models, having more growth in the second half of the year from those products is important. Uzaira continues to be a strong driver of growth for us and expect that to continue in the second half as well.

Thanks so much for taking our question. Thanks, Anupam.

Thank you. We will now take our next question from the line of Igor Notomovic from Citigroup. Please ask your question, Igor.

Yeah, hi. Thank you very much. I had a bunch of questions on the BEMA topic. So obviously you can't tell us the data, but you have said that it's statistically significant and clinically meaningful. And obviously in FITE, in the Phase II FITE trial, the OS delta was over 13 months. So can you just help put in perspective what the expectations should be around the OS data for 42-101 in terms of the expected delta? And then for 102, given that it's with NEVO, I'm also curious whether you would expect that the delta would be less because you have NEVO on both sides of the equation, and then Also, in China, what's going to be the regimen that is more likely to get the uptake in gastric? Is it with the chemo or also with the NEVO? Thank you. And then I have another one on DLL3. Thank you.

I'll ask Rafael to jump in here on the question. Thanks.

Yeah, I mean, I think with regards to the magnitude of the treatment effect, I'm afraid I can't comment because it's embargoed until the presentation, obviously. But I think other than the qualitative statements that Anjan and I have made with regards to the clinical meaningfulness of the differences between placebo and BEMA, I can't really say very much more. And so stay tuned for that. I think with regards to the differences in survival between what is seen in 101 and 102, again, I would be speculating. The difference in survival of neoengastric and G junction tumors is not very pronounced. As you know, it's about a couple of months or so. You know, if one maintained, you know, the same sort of survival difference with BEMA, You know, you could potentially have an additive effect to those two months, but again, difficult to speculate. And we will know when we see, you know, when we see the data. And then in terms of uptake in China, it's difficult to tell, but the 101 is a particularly important study for us in China. The use of NEVO is relatively low, but there are other PD-1 inhibitors, and many patients are treated without PD-1 as well. And so chemotherapy plus VEMA, if it's perceived to be a very important advance, it will be used. So it remains to be seen how much traction the PD-1 inhibitor will have. But, you know, there will be a difference in time also of the launch of one versus the other, which may affect as well uptake of a potential PD-1. So I'm afraid I can't really give you a concise and accurate answer, but this is sort of my qualitative statements.

Okay, all right. And then for the DLL-3, so it looks like you're somewhere in the 1.6 mg per kg for the dose that you've done so far. So with the combo with the Tezo, how are you thinking about the combo dose for DLL-3? Do you think you can stay at the 1.6, or may you need to be a little lower potentially for ComboTox, or do you see that it's not you're not going to have, you know, overlapping toxin. It's fine just to go with what you saw already in the monotherapy?

It's a bit premature to say with certainty, but the toxicity of these two agents are very different, and actually a 1.6% 1310 is very well tolerated. We only had 6%, grade three and above. And so with the non-overlapping toxicities, we believe that the combinability with 1.6 is very possible, and we're working towards that. And then in addition to that, we're also trying to do an etoposide sparing regimen as well, and we continue to study the triplet with CARBO. So all this data will, as it matures in terms of follow-up and response and safety, we will present it most likely in the first half of next year.

Okay, and if I could have one for Josh. Josh, obviously there's a lot of momentum with FGAR, but you have these four new experiments the lupus, seronegative GMG, myasthenia gravis, Soren's disease. I'm just kind of curious, when you put all those together, how does that change your perspective on the potential overall peak for this drug relative to the initial rollout of indications? Can you just kind of frame that so we can get sort of a zip code of how much more that's going to drive the overall franchise long-term? Thank you.

Sure. Thanks, Egal. You know, first, you know, we've said consistently that over time we see a greater than billion dollar sales potential on an annual basis in China for VivGuard when you look at the various indications, and I think we're Certainly on the way there, of course, you know, today the opportunity is to drive penetration usage and duration in GMG. But I think if you look at the indications you mentioned, certainly those that are complementary in the GMG space can add, you know, somewhere, you know, in the range of 25% or more, you know, sort of patient opportunity within GMG. So this, you know, this would be ocular and seronegative. lupus, you know, we're, you know, excited to see the data. That's a very, you know, big potential indication, but still, you know, still more to come. I think myositis and sorghans, again, also pretty big indications. So I think if you look at the total patient population, then add in thyroid eye disease, You know, we go from a starting point of about 170,000 patients with GMG in China to something well over 500,000 when you start to put these indications together. So, you know, as we've said, the billion dollar type of opportunity, you don't have to assume, you know, huge penetration rates or otherwise. And again, I think the data that we've seen so far that have been released, you know, give us a lot of confidence that there's going to be significant benefits across the various indications here. But for us today, it's drive penetration in GMG, look forward to the supplementary indications that can build out that patient population. For 2026, get Hytrulo approved through NRDL. We think that'll bring significant patient benefits. Then supplement that with the pre-filled syringe, which we'll work towards submitting later this year. So a lot to come in VivGuard and a lot to be excited about in terms of the current performance and things to look forward to.

Got it. Okay. Thank you very much.

Thank you. As a reminder, before we take our next, it is Star 114 questions. We will now take our next question from the line of Tzu-Yi Chen from Goldman Sachs. Please go ahead, Tzu-Yi.

Hi. Thank you for taking my questions. Two questions for me. The first one is for VivGuard. I understand that as you mentioned, in first quarter, there has been some inventory management that lead to weaker sales. And I'm wondering, was Vivacar still under this type of inventory management in the second quarter? And how should we look into the second half, and particularly in July, what has been the momentum versus previous months in the first half? And also, we look at Arginax, they observed very strong sub-Q formulation uptake. and what will be the strategy in China between sub-Q and IV formulation for Vivgar from your perspective. And my second question is regarding the DL3-ADC. Now the asset's going to be moving to pivotal study pretty soon. So at this juncture, we're trying to understand a bit more about the competition strategy in the U.S. market. Are you still actively looking for a partner for clinical development? or the strategy is going to be pivoting towards self-sponsoring the pivotal study and potentially the future commercialization to capture all the economics. Thank you.

Thanks. I'll start on DevGuard and then turn it to Rafael for the discussion on DLL3. I think first on the inventory piece, you know, I just would remind you that in, you know, 2024 was our first year of launch, and as you would in any you know, new launch product on NRDL. We, you know, built inventory through the year to keep up with demand. And at the end of Q4, stocked the channel for the approval of HyTRULO. So you do have some inventory, you know, build in the 2024 numbers, again, as you would expect. I think first half of this year for VivGuard, we tried to manage that inventory closely. And I would say in the second half of the year, you should expect normal types of build to prepare for 2026 and what we presume will be robust sales, including, as I mentioned in the last discussion or question, our expectation that HyTRULO will be added to NRDL. And then I think to your question, I think from what we see around the world where HyTRULO is available, it becomes, you know, a very important treatment option and treatment choice relative to IV. So, I think we would expect over time that HyTRULO would become a very meaningful formulation for patients with the GMG, and we'll, again, we'll pursue in our DL appropriately in that regard. So, I think as you get into 2026, you should expect to see, you know, a shift from, of course, today almost exclusively IV use to significant HyTRULO and then, you know, certainly followed in the coming years by the PFS version as well. I'll ask Rafael to comment then on DLL3.

Yeah, so with regards to the appealable trial, we have said before that we've been in discussions with FDA and this accelerated approval pathway is still viable. It will be a randomized trial and we're on track to initiate this trial before the end of the year. We have to align on the dose, but as we presented our last code, 1.6 mg per kilogram is looking very strong and probably the best sort of combination and benefit-risk. We will continue to generate data. We will present some data as well on the durability, but our goal is to get agreement on the dose and initiate this trial, and, you know, with regards to partnership, you know, initial pursuit is going to be to go ahead and launch this trial ourselves. And, you know, the discussions, I think, may remain open, but we're pretty committed to moving this forward by ourselves, and this study will be launched by us.

Got it. Thank you.

Thank you. Our next question comes from Lee Watson from Kantor. Please go ahead, Lee.

Hey, good morning, guys. Thanks for taking our questions. I have two pipeline questions. First on FEMA, just wondering what steps are left to file in China, and is it possible to get an RDL listing in 2027, or should we assume it's more of a 2028 event? And then for DL3 ADC, how are you guys thinking about the data from Henry DL3 program next month? Any research you're on program? And for data update later this year, what additional information do you hope to share relative to the ESCO update?

Thank you.

Thanks, Lee. I think first on BEMA, you know, and Rafael can provide some more comments here, but our focus now is to, you know, get the file submitted and approved. And, you know, as you know, NRDL timing, you know, is dependent on when you're approved during the year, and that always changes and everything else. So, we're just focused right at this point on getting that product approved as quickly as possible, and then moving as quickly as possible into NRDL listing. So, we'll have more to, you know, more to come there as we move through the regulatory process. I think, Rafael, if you could jump in on both of the questions.

Yeah. So, with regards to BEMA, we have breakthrough designation, and we will be working with Amgen, our partner, in potential registration in China expeditiously. We obviously will have to do a pre-VLA meeting and get feedback from CVE. And so this is a priority for us. And again, we're in discussions with Angen as to the initiation of the submission. With regards to the competition from Hungary, Yeah, well, we know, I think, what everybody knows, which is that they're presenting a war lung later on next month. And I would just only highlight the fact that products, especially ABCs, can be differentiated by many factors, including the type of antibody, the epitope, the ability, the payload, the linker, et cetera. We think that we have the best in class antibody, as we showed at ASCO a couple of months ago, with 79% response rate, which is, yes, confirmed and unconfirmed, but among the highest that has ever been seen, and great activity in the brain as well. And we are really advanced already with regards to, you know, getting the dose ready for execution of the phase three study, as I mentioned before. So we have, you know, a good time difference with regards to the competition. And in terms of what we will present, there will be another four months' worth of data, which will include updated response and time-to-event endpoints, both durability of response as well as progression-free survival. And importantly, we're characterizing these responses in the brain because they are really unprecedented, and it's something that we're hearing a lot from our investigators in terms of the high incidence and the durability So, you will see which is the way that brain metastases are assessed as well as response for the brain metastases in the totality of the population. And we may present some data on biomarker as well. But I think the principal update will be updated responses on the dose optimization as well as durability.

All right, thank you.

We will now take our next question from the line of Jack Lin from Morgan Stanley. Please go ahead, Jack.

Hi, thank you for taking my question. I have two brief questions. First one regarding the DIL-3. I just would hope to, I think, clarify a bit on the catalyst with data timeline. So if I could confirm again in terms of when we might expect the next data update from the second line treatment and especially I think on the expenditure covert. And also I think it was mentioned previously at the ASCO call, you know, we also have first line data upcoming. I just like to reconfirm on the timeline to expect for that. And a second one, I think on briefly on whether the company has review or update in terms of, you know, some of the policy news update regarding commercial insurance ramp up and if there's any implications or, um, changes to our commercial strategy for products like Optune? Just these two questions. Thank you.

Rafael, why don't you go ahead?

Yeah, so for DL03-1310, we expect to provide this update before the end of the year on the second line, as you mentioned, and I explained before what the nature of the update will be. We had 89 patients at ASCO. Here, we will have upwards of 110 patients and, obviously, four more months of follow-up, as I mentioned. With regards to first-line, because, you know, we are prioritizing the second-line study, we continue to enroll in the first-line cohorts, both with ADESO and ADESO on cargo. If we have meaningful data, then perhaps it will be this year, but most likely it will be next year, early next year that we will provide that information. We are spending time enrolling in the second line and standing up the phase three study. So I hope this helps with the cadence of data. And then just to mention that we are doing well on the neuroendocrine carcinoma, neuroendocrine tumors. These are distinct cohorts, and we will provide an update as soon as we have meaningful information on that. But so far, the accrual has been very favorable, so we think that it will be relatively quickly. We want to wait until we see enough durability before we actually, you know, until we can present a meaningful update.

And Jack, I think on the commercial insurance policy changes, we're quite encouraged by the trend here. You know, keep in mind, I know you know this, you know, the reimbursement or funding for innovative drugs in China through a commercial insurance channel is considerably less than 10% today. So I think as we look at the policy changes to try to drive that number higher, it certainly benefits us as we launch new innovative products, not just Optune or TT Fields, but any of the products we've discussed today. There's always a lag between when they're approved through NMPA and when they are eligible for NRDL listings. So I think that time period, as commercial insurance expands, gives us a really good opportunity as we get drugs like BEMA approved or CARXT or others to leverage these channels and drive good experience and sales in that stub period between approval and NRDL listing. So, I think that's important. Certainly, as it relates to Optune and as we think about Penova or the opportunity in pancreatic cancer, I think that's one that's we'll certainly be able to time that well with some of these policy changes. So, again, I think it's positive for all companies who are bringing innovative drugs to market in China, and we look forward to participating and taking advantage of those policy changes.

Got it. Thank you so much.

Great. Thank you.

We have now come to the end of the question and answer session. Thank you all very much for your questions. I'd now like to turn the conference back to Dr. Samantha Du for her closing comments.

Thank you, operator. I want to thank everyone for taking the time to join us on the call today. We appreciate your support and look forward to updating you again after the third quarter of 2025. Appreader, you may now disconnect this call.

Thank you for your participation in today's conference. This does conclude the program. You may now disconnect your lines.