管理層發言
Hello, ladies and gentlemen. Thank you for standing by, and welcome to Zai Lab's Second Quarter 2026 Financial Results Conference Call. 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, ma'am.
Thank you, operator. Hello, and welcome, everyone. Today's earnings call will be led by Dr. Samantha Du, Zai Lab's Founder, CEO and Chairperson. She will be joined by Dr. Rafael Amado, President and Head of Global Research and Development; and Dr. Yajing Chen, Chief Financial Officer. Dr. Shan He, our Chief Business Officer; and Dr. Yizhe Wang, our Operating Partner, 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 6, 2026, 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.
Thanks, Christine. Good morning, and good evening, everyone. Thank you for joining us today. Zai Lab has reached an important inflection point in its evolution from a regional business into a global biopharmaceutical company. We built this company by bringing first- or best-in-class medicines to patients in China. Today, we are developing our own innovative medicines for patients worldwide with our first U.S. regulatory submission expected next year. The transformation reflects the R&D capabilities we have built. We're conducting global multi-center registrational oncology trials, advancing additional clinical programs across oncology and immunology and advancing our preclinical pipeline into INDs this year. Zoci, our potential first- and best-in-class DLL3 ADC, demonstrates what Zai Lab is capable of. We advanced it from IND to global pivotal trials in less than two years, reflecting the speed and efficiency of the integrated development organization we have built. By the end of this year, we expect to have three registrational programs in small cell lung cancer and neuroendocrine carcinoma. We're also evaluating Zoci in combination with T cell engagers through collaborations with Amgen and Boehringer Ingelheim. Our second major global opportunity is ZL-1503, a potential first-in-class long-acting IL-13/IL-31 bispecific for atopic dermatitis. We believe it has the potential to bring together multiple attributes in a single asset: robust skin clearance, rapid and durable reduction in symptoms, and a longer dosing interval. Later this year, we'll report the program's first human data. At the same time, we continue to strengthen our commercial business. This quarter, we sharpened our focus behind our highest-priority brands. Net product revenue grew 11% versus the previous quarter, and the business remained commercially profitable. We're setting a strong foundation and expect a return to meaningful year-on-year growth in 2027, followed by the potential for our first U.S. product launch in 2028. Zai Lab's evolution into a global biopharmaceutical company is well underway with a growing portfolio of globally developed differentiated medicines and a profitable commercial business. We're confident in the path ahead and the long-term value we can create for shareholders and patients. With that, let me turn the call over to Rafael to further discuss our pipeline in greater detail. Thank you.
Thank you, Samantha. Let me walk you through the pipeline and what to expect this year. Starting with Zoci, our DLL3-targeted ADC. Small cell lung cancer is one of the most difficult diseases in oncology, and Zoci has demonstrated what we believe is a potential best-in-class ADC profile. In patients who have failed frontline multiple lines of treatment, we're seeing strong responses, including high responses and control of brain metastases. That efficacy with a favorable safety profile positions Zoci as a backbone for future combination regimens across lines of therapy. This program is moving fast. Our global registration Phase III in second-line-plus small cell lung cancer is expected to complete enrollment in the first half of 2027 with a U.S. accelerated approval submission expected to follow later that year and approval anticipated in 2028. At ESMO in October, we will present combination data evaluating Zoci plus PD-L1 with or without chemotherapy in first-line small cell lung cancer or during maintenance. Today's standard of care of immunotherapy plus chemotherapy delivers a 60% to 70% response rate, median progression-free survival of about five months, and grade 3 or higher treatment-related adverse events around 60%. NCCN guidelines recommend four cycles of platinum-based chemotherapy. A chemo-sparing regimen could offer better tolerability, allow longer treatment duration compared to systemic chemotherapy, and improved control of brain metastases. This is the basis of our Phase III combination strategy with immunotherapy, which we have discussed with regulators. We anticipate initiating the trial in the coming months. In extrapulmonary neuroendocrine carcinomas, where there is no established standard of care in the second line and beyond, Zoci demonstrated a confirmed ORR of 38.2%, which is well above the roughly 18% seen with currently used regimens. We're engaging with regulators on a potential approval pathway using extended single-arm data from our ongoing second-line trial with a subsequent approval pathway in first line. So three registrational programs underway by year-end. We're also collaborating with Amgen and Boehringer Ingelheim to combine Zoci with T cell engagers. A global Phase Ib study with Amgen is already enrolling, including a cohort of untreated small cell lung cancer patients on a triple combination of Zoci, IMDELLTRA and Imfinzi. And the global Phase Ib/II study with Boehringer Ingelheim in neuroendocrine carcinoma is expected to initiate in the coming months. Beyond Zoci, our next wave of global assets is advancing quickly. ZL-1503 is a long-acting humanized IgG1 bispecific antibody targeting both interleukin-13 and interleukin-31 receptor alpha. It includes YTE amino acid modifications in the Fc region that extend serum half-life and support less frequent dosing. By blocking both pathways at once, ZL-1503 is designed to break the itch–scratch–inflammation cycle with rapid durable efficacy and less frequent dosing in moderate-to-severe atopic dermatitis. ZL-1503 is in the clinic now with first-in-human data in healthy volunteers to be presented in the second half of this year. This data set will include pharmacokinetic data following single-dose administration and pharmacodynamic data, including inhibition of AD-related biomarkers such as pSTAT6, TARC and CCL26, a cytokine that recruits eosinophils during type 2 inflammation. We will also have an initial read on safety and immunogenicity, including assessment of anti-drug antibodies. We're also currently enrolling patients with atopic dermatitis in the multiple ascending dose portion of the trial, and we will share this data at a major medical conference next year. We believe ZL-1503, with a potentially differentiated profile, can address unmet medical needs in one of the largest markets in immunology globally, and we are moving this program forward rapidly. Beyond its lead indication, ZL-1503 has the potential to expand into additional IL-13- and IL-31-mediated diseases, creating a broader development opportunity over time. We look forward to sharing updates as the program advances. I would highlight just two more programs: ZL-6201, our internally discovered LRRC15-targeting ADC. We are actively enrolling patients in the global Phase I study and expect to complete enrollment in the dose-escalation portion with initial data expected in the first half of next year. By year-end, we expect to submit an IND for ZL-1311, a next-generation T-cell engager targeting MUC17, a promising target for gastrointestinal cancers. In summary, we have the infrastructure and capacity to advance multiple global programs at different stages of development simultaneously, at speed and efficiency and across geographies, while also advancing our regional pipeline. We have significant data emerging throughout the year on our most advanced products, and I look forward to sharing it with you in the coming months. And with that, I'll hand it over to Yajing.
Thank you, Rafael. As Samantha and Rafael described, Zai Lab is entering the next phase of its evolution. From a financial perspective, our objective is straightforward: build on our commercially profitable business while investing with discipline behind the innovation that will drive our next stage of growth. In the second quarter, net product revenue grew 11% sequentially to $105.8 million, and the business remained commercially profitable. ZEJULA was steady. VYVGART volumes grew double digits sequentially. XACDURO demand remains strong despite supply constraints and KarXT's launch is off to an excellent start. In the second half of the year, we expect to further stabilize product sales while laying the foundation for a return to meaningful growth in 2027. KarXT is expected to be a key driver of that growth as the first new mechanism of action for schizophrenia in decades. With efficacy across positive and negative symptoms, no boxed warning, and inclusion in national treatment guidelines, we believe KarXT is well positioned to address a significant unmet need. Early physician interest and positive patient experiences are encouraging, and we are building good momentum ahead of potential NRDL inclusion in 2027. For the VYVGART franchise, we intend to seek NRDL inclusion for VYVGART Hytrulo and are preparing for a gradual transition from IV to subcutaneous formulation. As a result, reported revenue in the second half may not fully reflect underlying demand due to timing of NRDL-related commercial dynamics. Looking ahead to 2027, we are confident in a return to meaningful growth, supported by new product launches, potential NRDL product inclusion and continued demand growth across our key brands. Beyond 2027, we expect our internally developed pipeline to become an increasingly important contributor to both revenue and margins. On expenses, we remain disciplined, prioritizing our highest-value programs while improving productivity through streamlining the organization and the use of AI across clinical development, regulatory, commercial and corporate functions. As a result, we expect operating expenses to remain broadly stable through the remainder of the year. We ended the quarter with $717.5 million in cash, providing the financial flexibility to continue investing in the highest-value opportunities. Pulling this together, we have a commercially profitable business, disciplined capital allocation and a global innovative pipeline that will increasingly shape the company's future growth and drive substantial value for patients and shareholders alike. With that, I will open it up for questions.
分析師問答
We will now take our first question from the line of Anupam Rama from JPMorgan.
Just looking to ESMO, can you walk us through what you're looking for in the first-line small cell study of Zoci plus IO with or without chemotherapy? What is going to be the size and scope of that data set? And how are you defining a win scenario?
Thank you, Anupam. This is Christine. Rafael, could you take that question, please?
Sure. So at ESMO, we expect to present about 60 patients' worth of data. This will include doublet and triplet cohorts, but most patients will be in the doublet with a checkpoint inhibitor at the highest dose of 1.6 milligrams per kilogram. We have been monitoring that data and we think we'll be fairly mature by the time of ESMO with a median follow-up between eight or nine months. So we will be able to report on a meaningful data set by then. In terms of what to look for, the benchmark with the checkpoint inhibitor studies has shown responses in the 60% to 70% range with chemotherapy and median progression-free survival of about five months. So there's still room for improvement. An approximately 80% response rate and a 50% increase in median PFS would be, I think, clinically meaningful. So those are the parameters that we're looking for. We're, at the same time, preparing and operationalizing the study. It's going to be a chemo-sparing study, not because we saw any dose-limiting toxicities with the triplet, but because we think it's more convenient, and we will be able to give higher dose intensity of Zoci than chemotherapy allows.
And the next question comes from Michael Yee from UBS.
This is Kyle Yang for Michael. Two questions for us. The first one on a higher level: the company previously guided toward profitability by the end of 2025. How should we think about that? At what point do you think investors can start to revisit the profitability goal? The second question is on IL-13/IL-31. The atopic dermatitis landscape is getting increasingly competitive. We recently saw additional investor interest in the space, including a new IPO this week that also has an IL-13/IL-31 asset. How should we think about the differentiation of your asset versus competitors?
Thank you, Kyle. Yajing, can you please take the one on profitability and Rafael, a question on the differentiation of 1503, please?
All right. Thanks for the question. I'm looking at profitability through the lens of our capital allocation. We already have a commercially profitable business today. Our local manufacturing is on track for XACDURO and KarXT, which will continue to improve our profitability. However, at the same time, we have multiple global competitive programs that we believe have the potential to create substantially greater long-term value. Right now, our responsibility is to invest where the returns justify it. We maintain a very high bar for every investment decision. In summary, we expect growing revenue with our potential global approval in 2028, which will improve margin and drive operating efficiencies across the organization. Those factors together will naturally lead to improved profitability over time.
Yes. I'll make a few comments about ZL-1503. The molecule is designed to have three highly desirable attributes. First, robust skin clearance, which we expect through type 2 suppression and by breaking the cycle of itching, scratching and inflammation. By inhibiting the IL-31 receptor, we should see brisk reduction in pruritus. Second, the molecule is YTE-modified to extend dosing interval; that is being tested in the current studies in healthy volunteers and in multiple ascending dose cohorts, and we expect that it will be superior to current standards, which are often monthly or every two weeks dosing. We expect to go beyond that. Third, we expect simultaneous improvement in itch and underlying inflammation because we're targeting IL-13 ligand and IL-31 receptor. There are a few agents in development that have some of these attributes; some are preclinical, some target the ligand, some the receptor. We believe our combination of targeting IL-13 ligand and IL-31 receptor plus YTE modification will result in better outcomes for pruritus and inflammation. This is an underpenetrated market where there isn't a single winner-takes-all outcome, so improvements in quality of life, extended dosing, and improved inflammation and symptoms will allow drugs to have a role. We're moving fast in Phase I: we expect to present healthy volunteer data this year and MAD data in atopic dermatitis next year, so we are somewhat ahead of some competitors.
We will now take our next question from Li Watsek from Cantor.
I have one pipeline and one commercial question. For ZL-1503, the bispecific antibody, what is the potential dosing profile that you're looking for? How would the single-ascending-dose data later this year inform you on the drug profile? Any early trends on anti-drug antibodies from the MAD cohort? And the second question is on the commercial side: at a high level, how do you envision the China business evolving in the coming quarters? What are the metrics that are most important to you?
Thank you, Li. Rafael, can you take the question on the dosing profile for ZL-1503 and how the upcoming data will inform the profile and on ADA? And Yizhe, if you can address the commercial question, please.
Yes. In the healthy volunteer single-ascending-dose study, it's a single intravenous injection with six cohorts testing four doses. The single injections are followed long term. This will inform us mostly on tolerability and pharmacokinetics, including half-life, and on the biomarkers I mentioned in the prepared remarks, including immunogenicity of anti-drug antibodies. The MAD portion has two cohorts with two doses, also IV, and it's a larger cohort. To hone in on the dose for the subcutaneous formulation, we will need more experimentation. There's a bioequivalence study planned to compare IV to subcutaneous, and then we'll do more dose exploration with the subcutaneous route. We expect that there will be a short induction course followed by longer maintenance dosing, but it's premature to speculate on the exact dose. On the question about anti-drug antibodies, we are monitoring immunogenicity and will report the findings as the study progresses.
Hi, everyone. I'm speaking from China. First, I want to emphasize that our commercial view is not limited to China only; over a three-year horizon we have the potential to launch our first U.S. assets, including Zoci. That said, near term our focus is on the regional business, primarily China. We have a sizable business with a diverse mix — some CSO products and some promoted by our own sales team. It's important going forward to focus on three key brands: return ZEJULA to growth and continue volume growth for VYVGART, and deliver launch excellence for KarXT. From an execution standpoint, we must be brilliant at the basics and drive the metrics. The KPIs we focus on are underlying demand metrics such as new patient starts for each brand. For brands that have flattened, we want to return to growth; for those growing, we want to continue or accelerate growth. We have seen positive signals and expect stabilization of revenue in the next couple of quarters and a meaningful return to growth in 2027. In the upcoming quarter, after delivering 11% sequential quarter-over-quarter growth in Q2, I am confident we can solidify that improvement. During this period, we will also focus on NRDL negotiations and aim to win at good prices.
Our next question comes from the line of Yigal Nochomovitz from Citi.
This is Caroline on for Yigal. We're wondering, as your MUC17 T-cell engager approaches the clinic, what aspects of the preclinical profile give you the greatest confidence it can overcome historical challenges associated with T-cell engagers in solid tumors?
Rafael, if you can take the MUC17 T-cell engager question, please.
Sure. MUC17 is an interesting target in GI tumors, notably gastric, pancreatic and other GI tract tumors. The molecule is engineered to be biparatopic, targeting more than one epitope, which should increase avidity. The CD3 binding arm is balanced with a higher on/off rate, which we believe may ameliorate cytokine release syndrome, the Achilles' heel of these products that often necessitates hospital administration. Much of the innovation in the T-cell engager field is directed at increasing efficacy while decreasing CRS-related toxicity so these agents can ultimately be given in the community. Preclinically, as we prepared the IND, the product shows favorable properties compared to other candidates targeting MUC17, and we are excited to move forward with the goal of filing the IND by year-end.
We will now take our next question from Daina Graybosch from Leerink Partners.
I wonder if you can talk about the combination of your DLL3 ADC with the DLL3-targeted T-cell engager and sort of mechanistically and biologically why that has value or differentiation relative to combining a DLL3 T-cell engager with the B7-H3 ADC?
Thank you, Daina. Rafael, can you address the question on the combination of DLL3 ADC plus T-cell engager and why it may have value and differentiation versus the B7-H3 combination?
Yes. The more straightforward reason is that the mechanisms of action are orthogonal and complementary. An ADC is cytotoxic and can debulk tumors — particularly in small cell lung cancer, which can present with high tumor volume — and that debulking can allow T cells to eliminate residual disease and maintain immune surveillance. As the ADC kills tumor cells, it liberates other antigens, including neoantigens. T cells, even if directed to DLL3, can respond to these liberated antigens, particularly when combined with PD-1 or PD-L1 blockade. In the case of Zoci and IMDELLTRA, the epitopes are different, so both drugs can bind the same cell. ADCs can have activity even at lower receptor densities through a bystander effect, which can complement T-cell engager activity. These hypotheses still need clinical proof, and the initial studies are aimed at evaluating tolerability. The encouraging part is there aren't major overlapping toxicities aside from potential myelosuppression. Regarding target selection, B7-H3 is not tumor-specific and is present in normal tissue such as lung epithelium, which could increase toxicity; lung toxicity is a real concern in small cell lung cancer given the incidence of ILD with some ADCs. A more tumor-specific target like DLL3 may therefore be a safer option. We look forward to results from the various combinations, and we hope to have data early next year.
We will now take our next question from Linhai Zhao from Goldman Sachs.
This is Linhai from Goldman. Just a follow-up on the Zoci and DLL3-TCE combinations. We've seen that both Amgen and Boehringer Ingelheim have initiated Phase I/II trials, including cohorts for both later lines and first line. For the RP2D in first-line triplet exploration, will the RP2D remain at 1.6 milligrams per kilogram, or will there be dose titration to a different level? For the two Phase I/II trials, when might we expect to see some data?
Thank you, Linhai. Rafael, could you address the RP2D dose question for Zoci plus T-cell engagers?
Yes. For the combinations, the immunotherapies — whether PD-L1 inhibitors or T-cell engagers — will generally be used at their standard doses, although there may be scheduling accommodations to align with Zoci's three-week dosing interval. For Zoci itself, we're currently exploring two doses and moving fast: 1.2 and 1.6 milligrams per kilogram. We don't have any reason to think 1.6 won't be well tolerated, so we hope that will be the dose used in expansion cohorts and across the development plan. The Amgen study is enrolling well and includes an untreated cohort, which is particularly exciting. As you know, response rates with T-cell engagers alone have tended to be more modest — in the 30% to 40% range — while ADCs show higher response rates. Combining different response profiles, durability and potential immune surveillance could be advantageous. We hope we won't need to change the target dose of 1.6 milligrams per kilogram for Zoci.
And when should we expect data readouts from the combination trials?
The Amgen-led study is operationalized by Amgen, and while we work closely with them, they will lead decisions on timing of public disclosures. My sense is that we may see data next year, likely in the second half, but I can't provide a definitive date.
I am showing no further questions. I'll now 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 2026. Operator, 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.