Zai Lab Limited

Hello ladies and gentlemen, thank you for standing by and welcome to ViLab's third quarter 2024 Financial Results Conference call. At this time all participants are in a 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 Xiao, Senior Vice President of Investor Relations.

Please go ahead.

Thank you, Operator. Hello everyone and welcome to ViLab's third quarter 2024 earnings call. Today's call will be led by Dr. Samantha Dew, ViLab's founder, CEO and chairperson. She will be joined by Josh Smiley, President and Chief Operating Officer, Dr. Rafael Amato, 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 November 12, 2024 for additional information on this non-GAAP financial disclosure. At this time, it is my pleasure to turn the call over to Dr. Samantha Dew. Thank you,

Christine, and welcome everyone. This has been a tremendous year for ViLab as we continue to execute our three key strategic priorities, driving revenue growth, expanding our global pipeline, and enhancing operational efficiency, starting with revenue growth. Total net product revenue for the third quarter grew 47% year over year. Our commercial business in China is growing rapidly, with Vivgard on track to become one of our potential blockbuster products. Later this year, we expect to launch multiple new products and invitations, which will further grow our top line. Turning to our pipeline, we've made significant advancements in our global pipeline. Recently, we presented data from CL1310, a potential -in-class CL L3 targeted ABC, an extensive-stage small cell lung cancer. We also recently introduced our internally discovered L13, L31, by specific antibody for atopic dermatitis and other immunologic diseases. Additionally, we added CL6301, a preclinical role one ABC, which we plan to advance into phase one next year. By expanding our global portfolio, we are not only addressing pricing halter needs worldwide, but also reinforcing Zylab's role as an innovator in the industry. We also made substantial progress in our late-stage regional pipeline, keeping us on course for at least five potential approvals over the next one to two years. This includes CARXT, which we expect to submit to the NNPA in early 2025, and BMAT-2's map, where enrollment has now completed in both pivotal studies. These two products, which we believe both have blockbuster potentials, hold significant promise for patients and providers alike. Lastly, we are operating with increased efficiency and productivity throughout the organization. As a result of our efforts, we achieved a 40% improvement in net loss in the third quarter compared to the same period in the previous year. I'm thrilled about the progress we have made, and I want to emphasize that we are well-positioned to create substantial value for our business over the next few years. Thank you all for your continued support of our mission. I look forward to providing further updates in the coming year. Now I'll pass the call over to Josh. Josh?

Thank you, Samantha, and thank you everyone for joining the call today. This quarter we made great progress across our business, demonstrating strong financial performance and excellent execution across several pipeline programs. Our third quarter net product revenue grew year over year to $101.8 million, led by the successful launch and robust uptake of VivGuard and also supported by increased sales for Zajula and NeuZyra. Starting with VivGuard, the launch has performed exceptionally well across all measures, and we are on a clear path to exceed $80 million in sales, which is in line with our full year guidance. This would make VivGuard's launch in GMG one of the strongest ever for an immunology product in China. This achievement is driven by our team's ability to execute a strategic launch across the entire value chain. We start with hospitals, our primary channel for expanding patient access. I'm pleased to share that we've successfully achieved listings at all of our targeted top priority hospitals for the year, covering approximately 65% of GMG market potential. Now we are targeting the next wave of hospitals and enhancing supplemental insurance access to offer additional support for the patient community. Next, we place a core emphasis on physicians, where our scientific and data-driven strategies have proven effective. Physician awareness of the SCRN mechanism and the antibody-driven nature of GMG is growing. VivGuard's brand awareness and adoption have increased each quarter, and according to a third-party analysis by Ben Health, VivGuard is now the leading -of-mind biologic therapy for GMG alongside IVIG. Nearly 2,000 healthcare professionals in China have now prescribed VivGuard with a growing percentage now at 40% being repeat prescribers. This is a significant achievement given the early stage of the launch. Lastly, patients. Approximately 10,000 patients have now been treated with VivGuard since launch, and while this is an exceptional number, it is still just a new quarter. New patients continue to be added at a steady pace, and in the third quarter, we saw a substantial increase in the number of patients initiating treatment in the maintenance setting, whereas previously it was predominantly acute patients. Additionally, we are also seeing a significant increase in the number of repeat patients. Based on our estimates of the patients who initiated treatment with VivGuard in June, approximately one-third have already returned for the repeat cycle. Physicians are beginning to realize the value of long-term treatment with VivGuard for their patients. Over time, we believe patients should average five cycles of VivGuard each year, as we have seen in the ADAPT clinical trials. What we also saw from the ADAPT Plus trial was a distribution of patients based on the number of weeks that passed between the last infusion of the previous cycle and the first infusion of the subsequent cycle. Around 36% of patients waited less than six weeks, 37% waited nine weeks or more, and the rest fell somewhere in between. Now, while it's still too early to make any comments on the distribution in the real world setting in China, based on current trends and the positive feedback from physicians, we are excited by the strong momentum thus far. We also expect additional tailwinds for launch, including an anticipated update of the national GMG guidelines towards the end of this year, or early next year, which are expected to include VivGuard as an increasingly important treatment option for GMG. We also plan to launch VivGuard-Hytrullo, the subcutaneous formulation of F. cartigimod, in GMG by the end of the year. The shorter administration time of 30 to 90 seconds, as well as the possibility of self-administration, provides a significantly more convenient alternative to the IV formulation and will help drive further uptake. Demand for VivGuard is robust and growing, and we believe we are on our way to establishing a new standard of care for GMG patients to achieve better disease management. I'm also pleased to announce that earlier this week, the NMPA approved the supplemental biologics license application for VivGuard-Hytrullo for the treatment of adult patients with CIDP, only six months after the SBLA acceptance earlier this year. CIDP is a disease that affects 50,000 patients in China. There are no approved therapies for CIDP and we will be working to launch in this indication as soon as possible. Our VivGuard team is exemplary with -in-class support for our physicians, patients, and other key stakeholders, and this provides us with a strong footing as we look to execute on the launch of Hytrullo for GMG and CIDP. There are multiple additional opportunities for VivGuard, including the pre-filled syringe, which we expect to submit to the NMPA next year, and new indications, all of which Raphael will cover in his remarks. These opportunities will help us realize the great promise of VivGuard, which we believe can exceed $1 billion in annual sales in China and, importantly, improve patient lives. Now, looking at our other commercial products. Zajula continues to be the leading PARP inhibitor for ovarian cancer in hospital sales in China. We are seeing continued share uptake driven by increasing penetration in first-line BRCA-mutated patients. For NeuZyra, we continue to promote ongoing access and support for patients who rely on this important treatment. In addition to VivGuard-Hytrullo, we are also preparing for two additional launch opportunities. Ob-Tyro in ROS-1 positive non-small cell lung cancer, which comprises between 2 and 3 percent of the nearly 700,000 new cases of non-small cell lung cancer per year in China, and Zagdoro in hospital-acquired and ventilator-associated pneumonia caused by Acinibacter-Bimani infections, of which there are approximately 300,000 cases in China each year. Looking ahead, our late-stage regional pipeline is progressing nicely, and by 2026, we could see the launch of CAR-XT in schizophrenia and Bemirutuzumab in gastric cancer following closely behind. Both of these are substantial market opportunities, each of which represents at least $1 billion in peak potential. Furthermore, we expect to submit a BLA to the NMPA for TIVDAC and cervical cancer during the first half of next year, with plans to leverage our established Zagula Salesforce for its launch. We're on track to deliver significant top-line growth, and in parallel, we are also focused on driving efficient operations and financial discipline. Through our ongoing efforts on enhancing commercial efficiency, optimizing resource allocation, and increasing productivity throughout the entire organization, our net loss in the third quarter declined 40% -over-year. We are on track to reach profitability by the end of 2025, and a cash position of $716 million at the end of the third quarter allows us to prepare for the next phase of growth for ZyLab as we drive both revenues and profitability. In summary, our execution this quarter reinforces ZyLab's commitment to our strategic goals. With a strong product portfolio, expanding global pipeline, and targeted commercial efforts, we are well positioned to drive continued growth. We look forward to building on this momentum in the coming quarters. And with that, I will pass the call to Rafael. Thank you, Josh. As

Samantha highlighted, this quarter we made significant progress in advancing our pipeline, especially on a global scale with CL1310 and investigational DLL3-targeted ADZ. We are very excited by the preliminary clinical activities from the dose escalation portion of the ongoing Phase I study of ZL1310 in patients with recurrent small cell lung cancer, which we presented at the URTC NCIA-ACR or ENA symposium in Barcelona, Spain. CL1310 showed a robust 74% objective response rate across all those levels in patients with at least one post-treatment evaluation. While it is premature to assess durability, the response rate is the highest observed to date in second line and beyond in extensive stage small cell lung cancer, and among the highest with an ADC in any disease. The results also showed a 100% objective response rate in patients with brain metastasis, with all six patients achieving a partial response. One patient with prior indelible failure achieved a partial response with a 67% tumor reduction. Additionally, CL1310 demonstrated a good safety profile at all therapeutic dose levels, being well tolerated with the majority of treatment emergent adverse events or TEAEs being of grade one or two. Only 20% of patients had a TEAE being related to ZL1310, and there had been no adverse events leading to study drug discontinuation. Most of lung cancer is a highly aggressive disease affecting around 372,000 patients worldwide, including over 100,000 patients in the U.S. and Europe. The mortality rate is high with a five-year survival rate at just 5% to 10%, highlighting the clinical need for treatment against this aggressive, fast-growing neoplasm. With CL1310's early data demonstrating its -in-class potential, we have a great opportunity to significantly improve outcomes for patients with small cell lung cancer, and we will work to rapidly accelerate the development of this asset. To date, we have moved CL1310 swiftly into dose optimization for monotherapy and into dose escalation in combination with adzolizumab and adzolizumab post chemotherapy in the ongoing global phase one study for patients with extensive stage small cell lung cancer who had received prior platinum-based therapy. DLL3 is also highly expressed in other neuroendocrine tumors, and we will start a global study next year to explore CL1310 in this indication. In immunology, we presented preclinical data on ZL1503 at the European Academy of Dermatology and Venerology Congress, or EADV, this year. This is an IL-13 IL-31 bispecific antibody internally discovered by ZY, which we aim to develop in atopic dermatitis and other inflammatory and pruritic conditions. We continue to see promising results of this bispecific in preclinical models, and we expect to share more details at a medical conference in 2025. We expect to submit an IND application to the FDA next year. In oncology, we're planning to initiate a global phase one study in soli tumor next year with ZL6301, a next generation ROR1 ADC program. We will leverage our strong capabilities to develop these assets as quickly as possible, and we anticipate continuing to expand the internal pipeline and progress other undisclosed global products into IND enabling and IND submissions next year. Now moving on to our key late stage programs, starting with neuroscience. Last month, we announced positive top line results on the safety bridging study evaluating the safety and efficacy of CAR XT in schizophrenia in China. CAR XT demonstrated a statistically significant 9.2 point reduction in PAN's total score from baseline at week five compared to placebo, with a p-value of 0.0014. The trial also met all the secondary endpoints demonstrating statistically significant reductions in positive and negative symptoms of schizophrenia as measured by the PAN's positive scale, PAN's negative scale, and PAN's negative mother factor score. CAR XT showed no unexpected safety signals. This data followed the U.S. approval of CAR XT announced by our partner, Bristol Mildersquid, in September. Not only the United States prescribing information of CAR XT or CoVenci does not list atypical antipsychotic class warnings and precautions, and does not have a box warning. In China, we will move swiftly to submit an NDA for CAR XT, this first in class central nervous system, spherinic agonism, schizophrenia in early 2025. Moving to oncology, we're making good progress with bimidizumab. And last month, we, along with our partner Amgen, completed patient enrollment in the 42102 study for bimidizumab in combination with chemotherapy and a checkpoint inhibitor as first line treatment for FGFR2B positive gastric cancer months ahead of schedule. Now we await results for both -to-studies, starting with 42101, which we expect in the next month. Next, with our immunology franchise. As Josh mentioned, we're excited about the recent NNPA approval of Viscar-Hytrullo, the subcutaneous formulation of F-CAR TG mod, for the treatment of adult patients with chronic inflammatory demyelinating polyneuropathy or CIVP. This approval brings a much needed novel treatment options for patients suffering with this progressive and debilitating neurological disease. The NNPA approval is based on the ADHEAR study, which we enrolled patients from Greater China. Treatment response in these participants was consistent with global study outcomes. The subgroup analysis of Chinese participants demonstrated a 69% reduction in the risk of relapse with Viscar-Hytrullo compared to placebo. Additionally, 78% of Chinese participants treated in the open-label period of the study demonstrated evidence of clinical improvement, further confirming the role of IgDG autoantibodies in the underlying biology of CIDP. The favorable safety and durability profiles of Viscar-Hytrullo weekly dosing in the Chinese patient cohort was consistent with that of the global participants. We appreciate the NNPA for their thorough assessment and recognition of the therapist differentiated profile and the large patient medical need in China. Beyond GMG and CIDP, we continue to work with organics to explore the potential to treat other IgDG-mediated autoimmune indications, including thyroid eye disease or TED, mucidus, seronegative GMG, ocular MG, and Sjogren's disease. We plan to participate in the global registration of studies for these indications, and we're initiating enrollment in these studies in China starting this month. I am excited about the great progress we're making with our regional and global pipelines, both in terms of the potential of the products to change medical care and the speed and quality with which we are executing both in discovery and development. I look forward to providing updates at our next earnings call. And now, Yejin will give an overview of our financial results. Yejin?

Thank you, Rafael. Now, I will discuss our third quarter of 2024 financial results compared to the prior year period. Total net product revenue for the third quarter was $101.8 million compared to $69.2 million for the same period in 2023, representing 47% -over-year growth. This increase was primarily driven by increased sales for Vivgard and also supported by increased sales for Zidula and Neuzeiwa. Primary drivers of this -over-year revenue growth included the following. Vivgard net product revenue grew to $27.3 million in the third quarter of 2024 compared to $4.9 million for the same period in 2023, driven by increased sales since its launch in September 2023, and NRDL listing for the treatment of GMG effective January 1, 2024. Zidula net product revenue increased 16% to $48.2 million. Zidula sales remain strong as continue to be the leading pop inhibitor in hospital sales for ovarian cancer in mainland China. Neuzeiwa net product revenue grew 82% to $10 million, driven by NRDL listings for IV formulation for the treatment of adults with community-acquired bacterial pneumonia or CAVP and acute bacterial skin and skin structure infections or APSE in the first quarter of 2023. And the oral formulation for these indications in the first quarter of 2024. Turning now to our expenses, research and development expenses were $66.0 million in the third quarter of 2024 compared to $58.8 million for the same period in 2023. This increase was primarily due to increased upfront and milestone fees for our license and collaboration agreements, partially offset by decreased clinical trial expenses and personnel costs as a result of ongoing resource prioritization and efficiency efforts. Selling general and administrative expenses was $67.2 million in the third quarter of 2024 compared to $68.6 million for the same period in 2023. This decrease was primarily driven by decreased personnel costs as a result of ongoing resource prioritization and efficiency efforts, partially offset by increased general selling expenses primarily for VVGuard. Last fund operations in the third quarter of 2024 was $67.9 million, $48.2 million on a non-GAP basis when adjusted to exclude non-cash expenses, including depreciation, amortization, and share-based compensation. Both narrowed by 19% year over year. We expect our last fund operations to continue to narrow as a result of growing revenues and ongoing cost and efficiency initiatives. Zylab reported a net loss of $41.7 million in the third quarter of 2024, or a loss per ordinary share attributable to common shareholders of $0.04, which improved by 40% year over year compared to a net loss of $69.2 million for the per ordinary share of $0.07. We are in a strong financial position, ending the quarter with a cash position of $716.1 million compared to $730 million as of June 30, 2024. Based on our operating plan and our anticipated new growth, we expect to be able to fund our business through profitability, which we expect to achieve by the end of 2025. And with that, I would now like to turn the call back over to the operator to open up lines for

questions. Operator. Thank you. We would now like to open the line for questions.

If

you have a question, please press star 1, 1 at this time. We will take our first question. Your

first question comes from the line of Michael Yee from Jeffreys. Please go ahead. Your line is open.

Great. Thanks. Congrats on the results and continued execution. We had two questions. The first was just thinking about Vivgard growth. Maybe Josh could comment, but you had significant growth in the first quarter, almost doubled in the second quarter and sort of more moderated in the third quarter. Can you just give some color about what would have driven third quarter growth and how to think about fourth quarter? And does it have to do with the timing of when people are getting the second cycle or how to think about the number of people coming back? Just maybe talk to the sequential growth that we were seeing quarter over quarter and in the fourth quarter. And the second question relates to obviously your DLL3 results, which got a lot of attention versus the existing approved job. Can you just remind us what the immediate next steps are and when we would get the next data released there? Thank you.

Okay. Hey, Mike. Thank you. It's Josh. I'll take the Vivgard question and then ask Rafael to comment on next steps with DLL3. I think with Vivgard, as I mentioned in the front remarks, we're really pleased with the first nine months of this year. I think in Q3, we saw continued trends in terms of about a thousand new patients being initiated per month. And increasingly, we're seeing because of where we are in the year and in the launch, we're seeing patients come back for second and third cycles. So really in line with what we would have hoped for and expected, I think in terms of the sequential growth, at some point, some of it just becomes a function of the base and where we are in the cycles and otherwise. And we, I think, I say, are quite pleased with Q3 performance. And I think as we think about Q4, everything we see so far, we're halfway through the quarter in terms of patient metrics and otherwise is very encouraging. We continue to see new patients come in at about a thousand a month. And increasingly, those patients are being initiated in the maintenance phase of the disease. You'll remember that we've focused in the second half of this year on really trying to get the patients started in a maintenance setting. These are patients that we consider uncontrolled, which is about 50% of the 170,000 patients in China. And if they're initiated in a maintenance setting, you have a really good chance to get them on average like five cycles per year over a calendar year. So I think we'll see in the fourth quarter, we should see the continued benefit from new patients coming in and the now building cumulative effect of patients coming back for second and third cycles. I mentioned in the comments up front that we can now look back to June as an example and look at the patients who were initiated then and sort of track them at a high level. And I think what we see is a third have already come back in for a second cycle and we should see more of that in the fourth quarter. So I think fourth quarter, no reason to not expect continued good patient capture and sequential growth. And I think we're really thinking now about 2025 and just sort of a reminder, I think if you look at number of patients that will be initiated on VivGuard by the end of the year, we'd expect that to be over 12,000. And if we can get some substantial portion of those patients into the maintenance treatment paradigm that we're focused on, I think you have a pretty good base of sales headed into 2025. Just as an example, if half of those patients are continuing on treatment in a maintenance phase, you're starting with a reservoir of somewhere in the range of $200 million or so of sales, which you've looked at patients on top of. That's not guidance or anything, but again, I think it continues to emphasize the good launch uptake that we see and long-term potential. I think with that, I'll turn it to Rafael to talk about the immediate next steps for DLL3.

Thanks, Josh, and thanks, Michael, for the question. I think it was about next steps and next sort of data set or update. So since the presentation, we've continued to enroll patients in other dose levels and of course, to capture durability. As you know, we talked about unconfirmed responses as well as a very short follow-up. So it's important for us to continue to see and let the data mature. We will continue also to have our own regulatory interactions, but at the same time, we've announced, as I said in the preparatory remarks, that we've chosen a couple of doses for dose optimization. So we'll start that randomization as well. We will decide when we have a meaningful update that may consist of the totality of the dose escalation with confirmatory responses on every patient and a decent follow-up across those cohorts and perhaps what we're starting to see in the randomization phase. So we are enrolling very fast and collecting data, and we anticipate that we will make this update sometime in next year. We haven't committed to a specific time, but it will be whenever we consider that we have a we're accumulating data fairly fast and that we're making significant progress with the study. It should not be very long from the last presentation. Thank you.

Thank you. Thank you. We will take our next question. Your next question comes from the line of Yigal Notchomovitz from City Group. Please go ahead. Your line is open.

Yeah, hi. Good morning. Thanks. There was some news yesterday, obviously, with regard to the schizophrenia market and the ABBEE data. Could you comment as to how that may impact your thinking about the CAR-XT launch given that change in the competitive landscape? And then more generally, just could you comment on the commercial buildout for CAR-XT as you proceed to launch the product? Thank you.

Thanks, Yigal. It's Josh. I'll cover this. First, we're quite excited about the opportunity for patients and for ZEI for RXT. And you've seen the results from the bridging study, which are very much supportive of and in line with global registration. So we're going to move fast towards the mission and get ready for launch. And I think for launch, I think one of the things that is different about China, I think, versus the US is the concentration of opportunity. I think we do see about 500 hospitals across China that comprise more than 50% of the 4 million patient type of opportunity that is resident in China. So I think we think of this launch in terms of the commercial buildout, at least initially, as closer to the VivGuard type of targeted approach than some of the broader launches, which you may be thinking about. So somewhere in the range of a 200-person Salesforce at launch should be able to capture much of the opportunity. We see the opportunity here as quite significant, as you know. And it's really around educating physicians, getting them to try CAR-XT versus the historical atypical antipsychotics. Of course, having less potential competition long-term is a good thing for our sales forecast and otherwise. But I think regardless, for the first few years, we were going to be focused on educating physicians on the new mechanism and the opportunity here. So that doesn't change. But certainly long-term, it provides a more open and broader field for us. So we've been consistent, I think, saying that we do see a quite significant opportunity in schizophrenia for CAR-XT. You certainly don't have to make very significant penetration types of assumptions to get to, at reasonable per-day prices, in line with what we see from post-NRDL branded atypical antipsychotics. You don't need to assume very high penetration rates to get to numbers that are in the billion-dollar range. So we're focused on capturing that opportunity and getting off to a quick start as soon as we can get submitted and approved.

Okay, thank you. That's super helpful. And then with regard to the internal discovery efforts, obviously you have the IL-13, IL-31, which you briefly mentioned. I'm curious how you're thinking about that one in terms of internal discovery versus potentially partnering that one out. And then also, if you have any updates on the topical IL-17, I'm curious how that one's going to evolve as far as the data.

Okay, great. Thanks. I'll ask Rafael to jump in on that question.

Yeah, thank you. With IL-1331, it's actually a product that will be an IND next year. We're pretty excited about what we're seeing proclinically with this product. It is a bi-specific, as its name implies, and we presented data in terms of its half-life, which is quite long, all into its special design of two heavy chains per binding site. Also, it's quite potent in proclinical assays, and we continue to do these assays over time to look at durability of the clinical effect. So far, we think it is the right ligand and receptor that chosen will provide an optimal molecule at least for eutopic dermatitis and other inflammatory conditions like potentially asthma, some eustenophilic disorders as well like hepatitis, as well as aortic disorders where there's a long list. So you're right. This would be a really massive development program. If we were to pursue all these indications, obviously we'll do this in a thoughtful way, probably starting with eutopic dermatitis and seeing how it performs in terms of long half-life potency, ability to dose long term, and ability to sort of literate the parietal sin-AID and then also affect the biology of the lesion, which is hopefully something that would lead to differentiation with regards to efficacy and safety and convenience. So those are my comments about these two products with regards to whether or not we will partner. Those are decisions that we haven't really evaluated yet around this product. We need more data about this. The other question was... Oh, I'm the IL-17. Oh yeah, IL-17. Thanks for that. So IL-17 is ongoing. It's testing two schedules and two trends against placebo in a phase two study, five arm trial, and it's growing quite well at the moment. We are going to start... We'll do an interim analysis for futility, and we think we'll have enough patient data sometime early next year. So I think the next data milestone, we'll probably just receive the recommendation from the IDMC on this utility analysis. And then after that, if the study continues and it will read out, we anticipate that we will complete a QO by the end of the year and then read out subsequently. So those are our plans. Whether or not there's a second interim analysis depends on what we are seeing or what the recommendation from the DMC is. But so far our plans are to do futility next year and then to continue if the futility is not met. Got

it. Thanks

very

much.

Thank you. We will take our next question. Your next question comes from the line of Anupam Rama from JP Morgan. Please go ahead. Your line is open.

Hi, guys. This is Priyanka An for Anupam. We just have a quick question. You guys have been increasingly highlighting the internal pipeline, and as you guys move to a more of a global infrastructure for clinical development, how should we think about R&D spend over the next several years?

We'll ask Yajing to cover that, please.

Hi, this is Yajing. Thanks for the question. So on the R&D side, as you know, we have a lot of regional pipeline in development right now. They are approaching to the approval stage. So that's a quite significant investment we made already, and that's continued to wrap up very quickly. At the same time, the global pipeline is picking up. So we are going to expect to expand and accelerate our global pipeline. In that position overall, R&D spend is going to remain relatively stable with modest growth in the future.

Gotcha. Thank you so much.

Thank you. We will take our next question. Your next question comes from the line of Louise Chen from Canter. Please go ahead. Your line is open.

Hi, team. Congrats on all the progress this quarter. Thank you for taking our questions. This is Wayne from Louise. So we have a quick question. What is the current competitive landscape for DLL3? Are there any other assets in development? And how should we think about the market opportunity and any type of ballpark potential revenue contributions you can think of? Thank you.

Thanks for the question. I'll ask Raphael to comment on the competitive dynamics in development in small cell lung cancer here, and then I'll come back and talk about how we think about market opportunities. So Raphael, if you want to give a quick summary here.

Sure. Yeah, it's a very dynamic and evolving field at the moment. You mentioned in development, there are two products approved that continue development, lorvinexidine, which is approved for progression after cisplatinum chemotherapy or after platinum therapy, and indeltra, which is a T-cell engager, DLL3 T-cell engager. Both were approved based on responses of 35 to 40% with durability 5.3 in nine months. So those are sort of the standards, if you will, contemporary standards for approval of these two drugs, and they both have post-marketing commitments for full approval. Other drugs in development, well, you may know about the ADC with Abbe from Grova T. That was actually discontinued because of toxicity, so that's not really in play at the moment. There are other T-cell engagers with ligand 2 DLL3, like BBI compound as well, and perhaps one that's emerging as a robust product is YL201 from MediLink, which was presented at ESMO, so V7H3 ADC, and it had a response rate in small cell lung cancer, 10 stage of 58%, closest six months of directional response in about 80 patients. So as you can see, the landscape is thankfully now robust with a number of products, both approved and in the process of development, and it's a good thing. We don't think that these products are necessarily cross-resistant, particularly T-cell engagers and ADCs or different targets like V7H3 and DLL3, as was mentioned in the preparing marks, so there were response, there was at least one response in Delta failure patients with our product with CO1310. So a dynamic landscape, but I think one that's much needed in this disease that remains strong on that need. I'll pass it on to you, Josh.

Josh Lerner Thanks, Rafael. I think given the unmet need here, we're quite excited about the market opportunity. This is a global asset for us, so if we think of patients in the West, it's about 100,000 patients with small cell lung cancer, and I'll focus my remarks on the US, which is about 40,000, because I think it can give an idea on how we see and think about the market opportunity. I think if we look at pricing in the range, and this is just looking at things like Tarlatum AbNOW and price per cycle, and you can extrapolate across other significant tumors otherwise, but if we use somewhere between $150,000 per second line, given number of cycles, and maybe $250,000 in first line, again, just very rough numbers, you can get using 40,000 patients in the US, if 25,000 of them are in first line, I think you can get to, again, using a $250,000 type of price, you get to over $5 billion in sales potential, and then in second line, if you're at 15,000 patients at fewer cycles, you can get somewhere in the range of $2.5 billion. We do see this as a $7.5 billion total market opportunity in the US alone, as Rafael mentioned, that's, they're not mutually exclusive opportunities here. We do see that as relevant for how we're thinking about developing DLL3 and the kind of exciting potential that is involved here. Of course, then you can extrapolate out to Europe and China and other markets as well, but we're quite excited, and of course, we'll put the investments in speed and execution around getting to the market so we can begin to tap into that opportunity.

Great, thank you so much. Thank you. Once again, if you wish to ask a question, please press star 1,

1 on your telephone. I am showing no further questions

at this time. I will now turn the call back over to Zylabs CEO, Samantha Du, for closing remarks.

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 fourth quarter of 2024. Operator, you may now disconnect this call.

Thank you. That does conclude our conference for today. Thank you for participating. You may now disconnect.