Zai Lab Ltd

HKEX:9688

Earnings Call Analysis

Earnings Call Transcript 2024-Q3

[Operator]

Hello, ladies and gentlemen. Thank you for standing by, and welcome to Zai Lab's Third Quarter 2024 Financial Results Conference Call. [Operator Instructions] As a reminder, today's call is being recorded. It is now my pleasure to turn the floor over to Christine Chiou, Senior Vice President of Investor Relations. Please go ahead.

[Christine Chiou, executive]

Thank you, operator. Hello, everyone, and welcome to Zai Lab's Third Quarter 2024 Earnings Call. Today's call will be led by Dr. Samantha Du, Zai Lab'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 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 Du.

[Ying Du, executive]

Thank you, Christine, and welcome, everyone. This has been a tremendous year for Zai Lab 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 VYVGART on track to become one of our potential blockbuster products later this year, we expect to launch multiple new products and indications, which will further grow our top line.



Turning to our pipeline. We made significant advancements in our global pipeline. Recently, we presented data from ZL-1310, a potential best-in-class DLL3-targeted ADC in extensive stage small cell lung cancer. We also recently introduced our internally discovered IL-13, IL-31 bi-specific antibody for atopic dermatitis and other immunologic diseases. Additionally, we added ZL-6301, a preclinical ROR1 ADC, which we plan to advance into Phase 1 next year. By expanding our global portfolio, we are not only addressing pricing health care needs worldwide, but also reinforcing Zai Lab'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 KarXT, which we expect to submit to the NMPA in early 2025, and Bemarituzumab, where enrollment has now completed in both pivotal studies. These two products, which we believe both have blockbuster potential, holds 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. And now I'll pass the call over to Josh. Josh?

[Joshua Smiley, executive]

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 47% year-over-year to $101.8 million, led by the successful launch and robust uptake of VYVGART, and also supported by increased sales for ZEJULA and NUZYRA. Starting with VYVGART. 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 VYVGART'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 FcRn mechanism and the antibody-driven nature of gMG is growing. VYVGART's brand awareness and adoption have increased each quarter. And according to a third-party analysis by Ben Health, VYVGART is now the leading top-of-mind biologic therapy for gMG alongside IVIg. Nearly 2,000 health care professionals in China have now prescribed VYVGART 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 VYVGART since launch. And while this is an exceptional number, it is still just a fraction of the 170,000 patients living with gMG in China. 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're also seeing a significant increase in the number of repeat patients.



Based on our estimates of the patients who initiated treatment with VYVGART in June, approximately one third have already returned for a repeat cycle. Physicians are beginning to realize the value of long-term treatment with VYVGART for their patients. Over time, we believe patients should average five cycles of VYVGART each year as we have seen in the ADAPT clinical trials. What we also saw from the ADAPT+ trial was the 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 VYVGART as an increasingly important treatment option for gMG. We also plan to launch VYVGART Hytrulo, the subcutaneous formulation of efgartigimod 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 VYVGART 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 VYVGART Hytrulo 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 in China, and we will be working to launch in this indication as soon as possible. Our VYVGART team is exemplary with best-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 Hytrulo for gMG and CIDP.



There are multiple additional opportunities for VYVGART, including the prefilled syringe, which we expect to submit to the NMPA next year and new indications, all of which Rafael will cover in his remarks. These opportunities will help us realize the great promise of VYVGART, which we believe can exceed $1 billion in annual sales in China and importantly, improve patient lives. Now looking at our other commercial products. ZEJULA continues to be the leading PARP inhibitor for ovarian cancer and hospital sales in China. We are seeing continued share uptake driven by increasing penetration in first-line BRCA-mutated patients. For NUZYRA, we continue to promote ongoing access and support for patients who rely on this important treatment. In addition to VYVGART Hytrulo, we are also preparing for two additional launch opportunities. AUGTYRO in ROS1-positive non-small cell lung cancer, which comprises between 2% and 3% of the nearly 700,000 new cases of non-small cell lung cancer per year in China; and XACDURO in hospital acquired in ventilator-associated pneumonia caused by Acinetobacter baumannii 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 KarXT in schizophrenia and Bemarituzumab 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 TIVDAK in cervical cancer during the first half of next year with plans to leverage our established ZEJULA sales force 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% year-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 Zai Lab as we drive both revenues and profitability.



In summary, our execution this quarter reinforces Zai Lab'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.

[Rafael Amado, executive]

Thank you, Josh. As Samantha highlighted, this quarter, we made significant progress in advancing our pipeline, especially on a global scale with ZL-1310, an investigational DLL3-targeted ADC. We are very excited by the preliminary clinical activities from the dose escalation portion of the ongoing Phase 1 study of ZL-1310 in patients with recurrent small cell lung cancer, which we presented at the EORTC-NCI-AACR or ENA Symposium in Barcelona, Spain. ZL-1310 showed a robust 74% objective response rate across all dose 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 metastases with all six patients achieving a partial response. One patient with prior in DELTA failure achieved a partial response with a 67% tumor reduction. Additionally, ZL-1310 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 1 or 2. Only 20% of patients had a TEAE being related to ZL-1310, and there has been no adverse events leading to study drug discontinuation. Small cell 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 ZL-1310's early data demonstrating its best-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 ZL-1310 swiftly into dose optimization for monotherapy and into dose escalation in combination with atezolizumab and atezolizumab plus chemotherapy in the ongoing global Phase 1 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 ZL-1310 in this indication.



In immunology, we presented preclinical data on ZL-1503 at the European Academy of Dermatology and Venereology Congress, or EIDV this year. This is an IL-13/IL-31 bi-specific antibody internally discovered by Zai, which we aim to develop in atopic dermatitis and other inflammatory and pruritic conditions. We continue to see promising results of the bi-specifics 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 are planning to initiate a global Phase 1 study in solid tumor next year with ZL-6301, 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 oral 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 from the Phase 3 bridging study evaluating the safety and efficacy of KarXT in schizophrenia in China. KarXT demonstrated a statistically significant 9.2-point reduction in PANSS score from baseline at week 5 compared to placebo with a p-value of 0.0014. The trial also met all secondary endpoints, demonstrating statistically significant reductions in positive and negative symptoms of schizophrenia as measured by the PANSS positive subscale, PANSS negative subscale and PANSS negative Marder factor score. KarXT showed no unexpected safety signals. This data followed the U.S. approval of KarXT announced by our partner, Bristol-Myers Squibb in September. Notably, the United States prescribing information of KarXT or Cobenfy 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 KarXT, this first-in-class central nervous system muscarinic agonist in schizophrenia in early 2025.



Moving to oncology. We're making good progress with Bemarituzumab. And last month, we, along with our partner, Amgen, completed patient enrollment in the FORTITUDE-102 study for Bemarituzumab 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 pivotal studies starting with FORTITUDE-101, which we expect in the next few months. Next, with our immunology franchise. As Josh mentioned, we are excited about the recent NMPA approval of VYVGART Hytrulo, the subcutaneous formulation of efgartigimod for the treatment of adult patients with chronic inflammatory demyelinating polyneuropathy or CIDP. This approval brings a much-needed novel treatment options for patients suffering with this progressive and debilitating neurological disease. The NMPA approval is based on the ADHERE 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 VYVGART Hytrulo 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 IgG autoantibodies in the underlying biology of CIDP. The favorable safety and tolerability profiles of VYVGART Hytrulo weekly dosing in the Chinese patient cohort was consistent with that of the global participants. We appreciate the NMPA for their thorough assessment and recognition of the therapy's differentiated profile and the large unmet patient medical need in China. Beyond gMG and CIDP, we continue to work with argenx to explore the potential to treat other IgG-mediated autoimmune indications, including thyroid eye disease or TED, myositis, negative CMG, ocular MG and Sjogren's disease. 



We plan to participate in the global registrational studies for this indication, and we are 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 pipeline, 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 Yajing will give an overview of our financial results. Yajing?

[Yajing Chen, executive]

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% year-over-year growth. This increase was primarily driven by increased sales for VYVGART and also supported by increased sales for ZEJULA and NUZYRA. Primary drivers of this year-over-year revenue growth included the following: VYVGART 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. ZEJULA net product revenue increased 16% to $48.2 million. 



ZEJULA sales remained strong as it continued to be the leading PARP inhibitor in hospital sales for ovarian cancer in Mainland China. NUZYRA 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 CABP, and acute bacterial skin and skin structure infections, or EPC, in the first quarter of 2023, and the oral formulation for this indication 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 were $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 VYVGART. Loss from operations in the third quarter of 2024 was $67.9 million, $48.2 million on a non-GAAP basis when adjusted to exclude noncash expenses, including depreciation, amortization and share-based compensation, both narrowed by 19% year-over-year. We expect our loss from operations to continue to narrow as a result of growing revenues and ongoing cost and efficiency initiatives. Zai Lab 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 same period in 2023 or a loss 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 revenue 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?

[Operator]

[Operator Instructions] Your first question comes from the line of Michael Yee from Jefferies.

[Michael Yee, analyst]

Congrats on the results and continued execution. We had 2 questions. The first was just thinking about VYVGART 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 great DLL3 results, which got a lot of attention versus the existing approved drug. Can you just remind us what the immediate next steps are and when we would get the next data released there?

[Joshua Smiley, executive]

Okay. Mike, thank you. It's Josh. I'll take the VYVGART question and then ask Rafael to comment on next steps with DLL3. I think with VYVGART, as I mentioned in the upfront remarks, we're really pleased with the first 9 months of this year. I think in Q3, we saw continued trends in terms of about 1,000 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 cycle. 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 1,000 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 5 cycles per year or 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 upfront that we can now look to -- back to June as an example and look at the patients who 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 as 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 VYVGART 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 look to add 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 the long-term potential. I think with that, I'll turn it to Rafael to talk about the immediate next steps for DLL3.

[Rafael Amado, executive]

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 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. And 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 meaningful update. We don't want to present just scanty data set. But given the fact that 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.

[Operator]

Your next question comes from the line of Yigal Nochomovitz from Citigroup.

[Yigal Nochomovitz, analyst]

There was some news yesterday, obviously, with regard to the schizophrenia market and the AbbVie data. Could you comment as to how that may impact your thinking about the KarXT launch given that change in the competitive landscape? And then more generally, just could you comment on the commercial build-out for KarXT as you proceed to launch the product?

[Joshua Smiley, executive]

Thanks, Yigal. It's Josh. I'll cover this. First, we're quite excited about the opportunity for patients and for Zai for KarXT. And you've seen the results from the bridging study, which are very much supportive of and in line with the global registration. So, we're going to move fast towards submission 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 U.S. 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 build-out, at least initially as closer to the VYVGART 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 sales force 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 KarXT 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, in saying that we do see a quite significant opportunity in schizophrenia for KarXT.



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 sales numbers that are in the $1 billion 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.

[Yigal Nochomovitz, analyst]

Okay. 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 is going to evolve as far as the data?

[Joshua Smiley, executive]

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

[Rafael Amado, executive]

Yes. Thank you. With IL-13, 31, it's actually a product that will be an IND next year. I would be pretty excited about what we're seeing preclinically with this product. It is a bispecific as its name implies. And we presented data in terms of its half-life, which is quite long, owing to its special design of two heavy chains per binding site. And also, it's quite potent in preclinical assays, and we continue to do these assays over time to look at durability of the clinical effect. So, so far, we think it is the right ligand and receptor that we've chosen will provide kind of an optimal molecule at least for atopic dermatitis and other inflammatory conditions like potentially asthma, some eosinophilic disorders as well like esophagitis, et cetera, as well as pruritic disorders where there's a long list, as you know.



So, you're right. I mean, 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 and probably starting with atopic dermatitis and seeing how it performs in terms of long half-life potency, ability to dose long-term and ability to sort of obliterate pruritus in AD, and then also affect the biology of the lesions, which is hopefully something that would lead to differentiation with regards to efficacy and safety and convenience. So those are my comments about these 2 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 -- yes, IL-17.



So, IL-17 is ongoing. It's testing 2 schedules and 2 strengths against placebo in a Phase II study, 5-arm trial, and it's accruing quite well at the moment. And 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 will probably just receive the recommendation from the IDMC on this futility analysis, and then after that, if the study continues and it will read out, we anticipate that we will complete accrual 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.

[Operator]

Your next question comes from the line of Anupam Rama from JPMorgan.

[Priyanka Grover, analyst]

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

[Joshua Smiley, executive]

I will ask Yajing to cover that, please.

[Yajing Chen, executive]

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 quite a significant investment we made already, and that's continued to ramp 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 net position, overall R&D spend is going to remain relatively stable with modest growth in the next few years.

[Operator]

Your next question comes from the line of Louise Chen from Cantor.

[Unknown Analyst]

Congrats on all the progress this quarter. This is Wayne on for 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?

[Joshua Smiley, executive]

Thanks for the question. I'll ask Rafael 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 opportunity. So Rafael, if you want to give a quick summary here.

[Rafael Amado, executive]

Sure. Yes, it's a very dynamic and evolving field at the moment. You mentioned in development, there are 2 products approved that continue development, lurbinectedin, which is approved for progression after cisplatin chemotherapy or after platinum therapy and in delta, which is a T-cell engager, DLL3 T-cell engager, both were approved based on responses of 35% to 40% with durability 5.3 and 9 months. So those are sort of the standards, if you will, contemporary standards for approval of these 2 drugs, and they both have post-marketing commitments or full approval. 



Other drugs in development, well, you may know about the ADC with AbbVie from Rova-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 to DLL3, like the BI compound as well. And perhaps one that's emerging as robust product is YL-201 from MediLink, which was presented at ESMO, a B7-H3 ADC and had a response rate in small cell lung cancer stage of 68%, close to 6 months of duration of 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 this is a good thing. We don't think that these products are necessarily cross-resistant, particularly T-cell engagers and ADCs or different targets like B7-H3 and DLL3. As was mentioned in the prepared remarks, there were response -- there was at least one response in delta failure patients with our product with DL-1310. So, a dynamic landscape, but I think one that there's much need in this disease that remains a strong unmet need. I'll pass it on to you, Josh.

[Joshua Smiley, executive]

Thanks, Rafael. And I think given the unmet need here, we're quite excited about the market opportunity. This is a global asset for us if we think of patients in the West. It's about 100,000 patients with small cell lung cancer. And if I'll focus my remarks on the U.S., 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 tarlatamab now and price per cycle, and you can extrapolate across other significant tumors and 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 to using 40,000 patients in the U.S. 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 or so billion. 



So, we do see this as a $7.5 billion sort of total market opportunity in the U.S. alone. As Rafael mentioned, 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.

[Operator]

[Operator Instructions] I am showing no further questions at this time. I will now turn the call back over to Zai Lab's CEO, Samantha Du, for closing remarks.

[Ying Du, executive]

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.

[Operator]

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