Hello, everyone. Welcome to BeiGene's Early Development Pipeline and Research virtual event. My name is Gabrielle Zhou, and I'm the Senior Director of Investor Relations at BeiGene. Today's presentation is being conducted entirely online with live translation, and it will be recorded and available on our website in both English and Chinese. During the presentations, all attendees will be in listen-only mode. After the presentations, we'll take questions from the audience. To ask a question, you will need to be joined to this call using a Zoom application on a computer or mobile device so that you can use the Raise Hand feature. If your audio connection to the call is via phone, please be sure you've joined via the Zoom application first, and then enter your participant ID on the phone. This enables us to properly get you unmuted. Please be sure your Zoom profile includes your full name. Before we begin, please be aware that during today's event, we'll be making forward-looking statements and our business carries certain risks. Some of these are discussed in our filings with the SEC and Hong Kong Stock Exchange. We have the great pleasure of having with us today both of BeiGene's co-founders, Dr. Xiaodong Wang and Mr. John Oyler. In addition to being our co-founders, Dr. Wang is the Chairman of our scientific advisory board, and Mr. Oyler is BeiGene's Chairman and CEO. In addition, we have our presenters, Dr. Lai Wang, Global Head of R&D, Dr. William Novotny, Head of Clinical Development of Hematology, and Dr. Yang Ben, Chief Medical Officer of Immuno-Oncology. We thank Dr. Novotny for standing in today for Dr. Jane Huang, Chief Medical Officer of Hematology, who is attending to a personal matter. During the Q&A, the presenters will be joined by Dr. Xiaobin Wu, President and Chief Operating Officer, Julia Wang, Chief Financial Officer, Angus Grant, Chief Business Executive, and Josh Neiman, Chief Commercial Officer for North America and Europe. I would like to introduce John Oyler, CEO and co-founder. John? Thank you, Gabrielle. Hello, everyone. We really appreciate you joining us today. I think as most of you know, Xiaodong and I started BeiGene 10 years ago. We had a belief in the power of science. We had a commitment to follow it, and we've invested heavily with that conviction from day one. From the beginning, there's been a thoughtful, science-led approach to everything that BeiGene's doing. With a clear goal of developing for patients impactful medicines that are more affordable and more globally accessible. We hope to share a bit more of our thinking with you today to help you understand what we are doing, why we're doing it, and how we've created strategic advantages that will help us achieve this vision. At BeiGene, we put patients first with an emphasis on two things, scientific excellence and affordability. Recently, the biopharm industry as a whole has been quite successful in developing impactful science, it has failed at affordability. Whether in the U.S., where 3 out of 10 patients are unable to complete treatment for economic reasons, or globally, where only three out of eight have access to innovative treatments. Medical inequity creates unacceptable problems. Xiaodong has been focused on how to create the elements that are required for scientific excellence, which is not easy, and for innovation. Meanwhile, I focus on business innovation, how to understand and analyze all elements of medicine discovery and development, and how to question and overhaul every aspect. Xiaodong and I believe that we simply cannot accept a world where so many patients cannot afford the benefits from science that could improve their lives or save people they love. Next slide, please. We started with the goal of scientific excellence, but also affordability, Xiaodong and I realized the following important things. First, over 75% of the cost of bringing a medicine to a patient and over 75% of the time is actually spent on clinical trials. It's amazing. The actual cost of goods sold is de minimis. Despite having these small costs of goods sold, only one-sixth of the world has affordable access. The upfront clinical cost burden has to be covered by much higher prices paid by the one-sixth of the world accessing that medicine. There's fewer patients to spread the costs. Third, clinical trials are lengthy and they're expensive. This is because they've largely been run in the top research hospitals in the richest countries, and it has resulted in lengthy enrollment times that are multi-year and of high costs. The fourth thing we realized was despite clinical science being the most critical element of the system, and one that you had to focus on given its predominant impact on cost and timing, typically, this is not something that companies have internalized. Most companies are relying on a handful of third-party CROs, and the net effect is widely recognized to be highly inefficient, expensive, and technologically dated. For example, some data from clinical trials might not be available within the clinical trial system for months. From the start, Xiaodong and I realized we had to do the following things to address these problems. First, we needed to internalize everything we could related to clinical trials. If you're not controlling it, you can't change it. Secondly, we need to work with regions that complement our U.S. and European trials by adding additional clinical science sites around the globe in places like China, Australia, New Zealand, Asia, and Eastern Europe, and work with these places. Third, develop and implement technology and operational excellence that modernizes the efficiency of clinical science. Xiaodong and my aspirational goal was to reduce time and cost by 50%. It was to create a new distribution model that would triple the number of patients who could access innovative medicines. If we could achieve these two things, the upfront cost per patient of a medicine would be reduced to one-sixth of historic costs. Certainly, we felt that was worth the effort. Next slide, please. Given our perspective, Xiaodong and I had been building BeiGene differently from day one. We're 10, 11 years in. The result is a compelling portfolio, an exceptional, fully integrated team, and sustainable competitive advantages. Our oncology research team has become one of the largest around without losing our culture of innovation, or our focus, or our passion. Our 1,700+ clinical team across the globe has already run large-scale global clinical trials and experienced two-thirds cost and two-thirds time. We're still improving. We've built large manufacturing resources in-house to secure capacity, to ensure flexibility, and to control cost. We've built one of the top oncology commercial teams in China. We're now becoming impactful commercial force in the U.S. and expanding in Europe. Soon you'll see us much further and much more broadly than most companies go across the globe. Today, BeOne Medicines is 7,000 strong, representing top talent on five continents with over 30 regional offices. We have the team. We have the competitive strategic advantages for the future. Now it is my enormous pleasure to introduce my good friend, Xiaodong, Dr. Xiaodong Wang, BeOne Medicines' co-founder and chair of our scientific advisory board. Thank you very much, John. It's my pleasure to join you here today. Your message, providing the best oncology medicine for the most people globally, highlighted the mission of BeOne Medicines. It is this mission that drives our R&D strategy and inspires our talented R&D team of more than 2,000 scientists and clinical development professionals to work hard every day. Next slide, please. Like John said, although oncology field has been in the midst of scientific revolution in the last decade, highlighted by tumor immunology therapy and targeted therapy, with significant improvement of patient's survival rate in major solid and liquid tumors. Cancer as a whole, however, still presents a major medical challenge for the drug development and the medical community. Last year alone, nearly 10 million deaths worldwide were still attributed to cancer. Therefore, although BeOne Medicines has been lucky to be born at the dawn of this oncology revolution, contributed with its own differentiated anti-PD-1 antibody and the best-in-class BTK inhibitor, we have been continuing to build up our R&D team to enhance our technology capabilities, to optimize our decision-making process. In the meantime, to maintain our entrepreneurial, inclusive, interactive, anti-hierarchical environment in which colleagues and ideas alike can thrive. As a result, BeOne Medicines now has a prolific pipeline, both at the preclinical and clinical stages, that rival big pharmas, addresses about 80% of the world cancer by incident. Additionally, as cancer treatment moves more and more towards precision medicine, a combinatorial approach for a group or even individual patients with a deep therapeutic agent toolbox has become essential. To be able to develop this oncology toolbox needs deep scientific understanding of the disease, technology prowess, culture innovation, as well as scale and operational efficiency that BeOne Medicines has and will continue to build. Today, you will hear some of the results of this effort from our Head of R&D, Dr. Lai Wang. More excitingly, such a platform will serve as our launching pad for BeOne Medicines to rocket upwards to serve our mission that John has just eloquently articulated. Now I'll give you our Head of R&D, Dr. Lai Wang. Thank you, Xiaodong. As John and Xiaodong just highlighted, BeOne Medicines is on a mission to bring innovative and affordable medicines to more patients around the globe. In order to achieve that, we have been focusing on building an R&D engine at scale to fuel innovation with efficiency and quality. Our preclinical research team has been highly productive with proven track record. In the past couple of years, it went through a major expansion. On the clinical development side, we are now largely CRO-free, with unique global operating model to drive speed and cost efficiency. Through our prolific internal discovery engine and external collaborations, BeOne Medicines has now close to 100 programs in our pipeline. BeOne Medicines's deeper portfolio provides a toolbox with ample tools for combinations, essentially centered around our two cornerstone assets, BTK and PD-1. BeOne Medicines's research team evolved through two stages. From 2011 to 2018, we were relatively small with around 150 to 200 scientists. It has a proven track record with three internally discovered medicines already on the market. However, due to the small scale, that team was only able to deliver one to two molecule clinic on a yearly base. In the past two years, the preclinical research team experienced a major expansion, triple size to 650 plus now, with plan to grow to 800 by the year-end. It is quite amazing growth, even when I look back at it. With that, BeOne Medicines will have one of the largest discovery teams in the world, mainly focused on oncology. Usually, expansion will lead to decreased efficiency or slowdown innovation. This hasn't been the case for us. Our discovery productivity has improved with new platforms, capability build-up, and portfolio management. There are currently 50 plus preclinical programs ongoing, including close to half with first in class potential. With this expansion, we do expect a burst of new molecules entering clinic in the next few years. To support this growing pipeline, we have also been building internal clinical development capability to run global clinical development with scale. Through the extensive internalization efforts in the last few years, we are now largely CRO-free. This is not a trivial undertaking, and it is not possible for small biotech without an unstable volume of clinical trials. The internal development capability gives us significantly better control on quality, speed, and cost, as well as site investigator engagement. BeOne Medicines currently has more than 1,700 clinical development colleagues around the globe, including close to 700 outside of China, and they expect to be over 2,000 by the year-end. We are also building an internal training academy to allow for continuous growth of this very high-quality team. Clinical development is the most expensive part of our industry and takes the most time. As shown in the two graphs on the left, cost and enrollment rates vary dramatically in different regions and countries. The graph on the top uses investigative fee as an example to illustrate per patient cost difference. The graph on the bottom shows patient enrollment rates in first line compared to our own China-only study number versus reference numbers from public database. BeOne Medicines's trial enrollment distribution is shown on the pie chart on the top right corner. The ratio is probably quite different from what you would typically see with the multinational big pharmas. We're enrolling around half of the patients in China and close to three-quarters in APAC region. This special composition of our clinical trial subjects under the internal capability to execute clinical trials in these regions allows us to run trials at around two-thirds of cost and two-thirds of the time. Meanwhile, we are committed to the highest quality standard with successful inspections by NMPA, FDA, Swissmedic, and our pharma partners. Our discovery engine has been productive since day one. In the first wave of internal discovered clinical molecules, three out of four are now on the market, helping patients around the globe. From 2016 to 2020, in the second wave, seven new molecules entered the clinic, many focused on combining with PD-1 or BTK. TIGIT is now at a pivotal stage, and we expect BCL-2 will be there soon. From 2021, we are in a new era to translate our science to novel medicines. We are more productive than ever with the upgraded discovery engine in both size and technology. Today, we will share with you the recent update for some of these programs, as well as the new exciting platforms. Meanwhile, BeOne Medicines is also enhancing innovation through various collaborations. For example, with our PD-1, tislelizumab, we're extending our existing franchise in large indications through novel combinations with cechervatimab, sitravatinib from Mirati, zanidatamab from Zymeworks, and the Leap Therapeutics assets. We are building collaborations with partners on next-generation technologies such as antibody drug conjugation, mRNA, and CAR-NK. Through both internal and external collaboration, BeOne Medicines has built a deep pipeline in which a total of 45 assets are at commercial or clinical stage. I'm going to hand it over to Dr. Bill Novotny, SVP for Clinical Development Hematology, to talk about our heme pipelines. Bill? Thanks, Lai. My name is Bill Novotny. I am the Senior Vice President of Hematology Clinical Development at BeOne Medicines. I've been with the company five years. Today I'm pinch-hitting for Jane Huang, our Chief Medical Officer for Hematology, who would usually give this talk. This slide shows BeOne Medicines's broad and deep hematology portfolio. Most people know we are deeply invested in the development of zanubrutinib in CLL and other B-cell malignancies, few appreciate our substantial development efforts in acute myeloid leukemia and myelodysplasia, as well as multiple myeloma through both internal discovery and external collaboration. Zanubrutinib was designed to overcome the shortcomings of ibrutinib. BeOne Medicines started with a hypothesis that improvements could be made upon ibrutinib to improve both safety and efficacy outcomes, improving safety by reducing inhibition of off-target tyrosine kinases and improving efficacy by complete and sustained BTK inhibition in leukemia and lymphoma tissue. In the clinic, zanubrutinib has demonstrated superiority over ibrutinib with better efficacy, better safety, and more convenience for patients. We have broad registrational programs ongoing for CLL, mantle cell lymphoma, Waldenstrom macroglobulinemia, marginal zone lymphoma, and other B-cell malignancies. The kinome analysis shown on this slide was conducted at an independent laboratory. First, the IC50 for BTK was measured independently for zanubrutinib, ibrutinib, acalabrutinib, and acalabrutinib's major metabolite, M27. Kinase selectivity was determined after adjusting the concentration of each molecule to 100 times each molecule's own IC50 for BTK. We believe this method provides a fairer and more accurate determination of selectivity for different BTK inhibitors as compared with using identical concentration of molecules regardless of potency. Each dot on the figure represents off-target inhibition of a kinase of more than 50%. In this analysis, zanubrutinib demonstrated higher kinase selectivity as compared with ibrutinib, acalabrutinib, and M27, potentially explaining zanubrutinib's excellent safety profile in the clinic. In the blood plasma of patients, zanubrutinib can maintain trough free drug levels sevenfold above the IC50 when dosed 160 milligrams twice daily and twofold above the IC50 when dosed at 320 milligrams once daily. In contrast, levels of ibrutinib, acalabrutinib, and M27 all fall below the IC50 line very quickly after reaching the peak of their pharmacokinetic curves. We believe this data provides a mechanistic explanation of why zanubrutinib is able to provide deeper and more sustained BTK inhibition, which should translate into better efficacy outcomes. The clinical development program of zanubrutinib for the treatment of various B-cell malignancies is broad and includes two large phase III head-to-head trials versus ibrutinib. To date, we have treated over 2,300 patients around the globe in BeiGene-sponsored clinical trials. Countries with either approvals, filings, and/or trials of zanubrutinib are shown in the bottom of the slide. The next few slides, I'm going to show you the results from our clinical trials of zanubrutinib in CLL, including the SEQUOIA, ALPINE, and AU-003 studies. These results validate our confidence in zanubrutinib as a treatment that can improve safety and efficacy outcomes for hundreds of thousands of patients living with CLL. This is a schema of the SEQUOIA study comparing zanubrutinib to bendamustine rituximab for standard chemo-immunotherapy in patients with treatment-naive CLL. Last month, BeiGene announced that the trial met its primary endpoint at an interim analysis, with zanubrutinib significantly prolonging progression-free survival compared with bendamustine rituximab. SEQUOIA was the second-positive global phase III trial of zanubrutinib in CLL following the ALPINE study. ALPINE is a randomized global phase III trial comparing zanubrutinib with ibrutinib in patients with previously treated CLL. Zanubrutinib met the primary endpoint of the trial, demonstrating superiority in overall response rate with a P value of less than 0.0001. The interim analysis from this fully enrolled ongoing trial is based on 415 of 652 patients followed for a minimum of 12 months. Analyses for progression-free survival and overall survival showed trends favoring zanubrutinib, even though the data was immature. We continue to follow the ALPINE study to the final response rate and progression-free survival analyses. This slide, I'm showing you our global phase I/II study, AU-003, with over three years median follow-up, in which we observed a landmark progression-free survival of 90.6% at 24 months and 82.8% at 36 months, suggesting a very durable clinical benefit in relapsed to refractory CLL. The AU-003 study began in 2014, It's very gratifying that we still have patients who started zanubrutinib in 2014 or 2015 and still continue to this day with disease control and very tolerable therapy. Next, turning to mantle cell lymphoma. At the European Hematology Association meeting this year, we presented long-term follow-up data from our 206 study showing a very high complete response rate of 77.9% and median progression-free survival of 33 months. Although there is limitation to cross-trial comparisons, other BTK inhibitors reported 13-22 months of median progression-free survival in relapsed refractory mantle cell lymphoma. This is consistent with our scientific hypothesis that complete and sustained BTK inhibition will result in improved efficacy outcomes. Moving to Waldenstrom macroglobulinemia, the ASPEN study is a randomized phase III trial comparing zanubrutinib with ibrutinib for the treatment of both treatment-naive and relapsed/refractory Waldenstrom macroglobulinemia. Zanubrutinib demonstrated a higher rate of very good partial response plus complete response and favorable trends in progression-free survival and overall survival. Unfortunately, the trial did not achieve statistical significance in its primary endpoint. This slide shows the safety overviews for our two trials that have head-to-head comparisons with ibrutinib. On the left is the ALPINE study in CLL, on the right is the ASPEN study in Waldenstrom. If you focus on the row showing adverse events leading to death and adverse events leading to treatment discontinuation, you see very consistent improvement in tolerability with zanubrutinib as compared with ibrutinib. Zanubrutinib has dramatically lower rates of cardiovascular toxicities as compared with ibrutinib. Shown here are time-to-event analyses. On the left are curves for time to atrial fibrillation in the ALPINE study in CLL. In the middle is the curve for time to atrial fibrillation in the ASPEN study in Waldenstrom macroglobulinemia. On the right are curves for time to hypertension in the ASPEN study in Waldenstrom macroglobulinemia. In addition to superior efficacy and safety as compared with ibrutinib, the clinical pharmacology profile of zanubrutinib translates into more convenience for patients. Zanubrutinib can be dosed at either 160 mg twice daily or 320 mg once daily. Zanubrutinib can be taken with or without food and has fewer drug-drug interactions, allowing it to be co-administered with a broader variety of concomitant medications. Zanubrutinib can be safely used in patients with renal or liver impairment. For example, zanubrutinib can be used in patients with severe hepatic impairment, while the ibrutinib label recommends avoiding use in that population. To provide access to many more patients, the global footprint of zanubrutinib continues to expand to more than 70 countries. In 2019, we completed 14 regulatory submissions for approval and received two approvals. In 2020, we completed 22 submissions. In 2021, we have completed 40-plus submissions and have 9-12 approvals expected soon. We are working hard to bring this best-in-class BTK inhibitor to more patients in need. To further strengthen our hematology portfolio, we are developing BGB-11417, an investigational BCL-2 inhibitor with potential best-in-class properties. The storyline around 11417 is quite like that of zanubrutinib. It is more selective and more potent than venetoclax, which we hope will translate into better efficacy and safety outcomes in the clinic. In addition, it has potential to overcome the resistance to venetoclax, which has emerged as a problem in the clinic. It has become a key molecule in our hematology portfolio, will be combined with zanubrutinib in B-cell malignancies, and provides an entry point to AML, MDS, as well as multiple myeloma. The dose escalation for 11417 is now ongoing for monotherapy of 11417, also in combination with zanubrutinib, also in combination with azacitidine. Clinical activity was observed at the first dose level of 40 milligrams. The PK exposure at 80-milligram level is equivalent to that of venetoclax at its CLL-approved dose of 400 milligrams. Currently, 11417 is being studied at the 320-milligram dose level, and pivotal studies are expected to be initiated in 2022. To summarize, for B-cell malignancies, we are building around zanubrutinib, our best-in-class BTK inhibitor. Results from large randomized clinical studies have supported our hypothesis that improvements could be made upon both safety and efficacy outcomes as compared with ibrutinib. We are exploring many combination opportunities, including with our own BCL-2 inhibitor, an inhibitor of PI3K delta, Revlimid, et cetera. Many new exciting molecules are coming in the pipeline, including BTK, CDAC, CAR-NK, bispecifics, ADC, et cetera. You will hear more about this later when Lai talks about the new modalities we are pursuing. We are also entering the AML/MDS space with potentially best-in-class BCL-2 inhibitor 11417, along with our growing pipeline, including agents targeting CD70, TIM3, CD33, FLT3, and MCL-1. With that, I conclude my section and would like to hand over the floor to Dr. Yang Ben, our CMO for immuno-oncology. Thanks, Bill. I'm going to walk you through our solid tumor portfolio. Through both internal discovery and external collaboration, BeiGene has built a deep and broad solid tumor portfolio, including multiple marketed products, ever-growing late-stage assets, a robust and diversified early pipeline that contains a wide range of modalities such as a small molecule, monoclonal antibody, bispecific antibody, ADC, et cetera. In the next few minutes, I'll walk you through some selected programs. Tislelizumab is a truly differentiated humanized IgG4 anti-PD-1 monoclonal antibody invented by BeiGene scientists, specifically designed to minimize binding to Fc gamma receptor, thus minimizing antibody-dependent cellular phagocytosis of PD-1, expressing T cells by macrophages. Therefore, maximizing T effector cells in tumor microenvironment. This scientific hypothesis was tested and further validated in clinical trials. In one of the tislelizumab phase II trials in patients with relapsed/refractory classical Hodgkin's lymphoma, showed impressive clinical activity with a complete response rate of 67.0% and median PFIs of 31.5 months. A beta limitation across health comparison, both CR rate and the median PFIs look quite favorable compared to data from other PD-1 antibody studies in the same setting and very similar population conducted around the same time as our trial. Interestingly, CHL is a tumor type that's enriched with macrophages. We have developed quite a broad clinical development program for tislelizumab. To date, tislelizumab has received five market approvals in China, including first-line both squamous and non-squamous lung cancer. Second-line, third-line urothelial carcinoma, second-line plus hepatocellular carcinoma, and the relapsed/refractory CHL. 4 supplemental BLAs are currently under review by the CDE. Moreover, there are 11 additional registrational trials ongoing or being planned, either as a monotherapy or in combination with our pipeline molecules. Seven of those as monotherapy or in combination with the standard care, I expect to read out in the next 36 months. Earlier this year, we announced the collaboration with Novartis on Tisla. It certainly opens opportunities for Tisla to combine with molecules in Novartis' robust oncology pipeline. To date, over 5,000 patients have been treated with Tisla on BeiGene-sponsored clinical trials, including almost 1,800 patients outside of mainland China. The collaboration with Brigham and Women's, one of the world's leading biologics manufacturers, ensures global manufacturing quality. Centered around PD-1, our strong solid tumor portfolio is being built based on solid scientific rationales. We are pursuing diverse mechanism actions that potentially can synergize with the PD-1 and/or overcome PD-1 resistance, including removing other checkpoint inhibition such as TIGIT and HPK1, directly activating T cells via agonists such as OX40 and bispecific antibodies, with T cell engagers. Inducing immunogenic cell death to enhance antigen spreading and presentation like lenalidomide and ZW49. Finally, reshaping immunosuppressive tumor microenvironment to overcome PD-1 resistance such as sitravatinib, TIM-3, PI3K delta, and so on. ociperlimab is another BeiGene in-house discovered monoclonal antibody against TIGIT. Similar to PD-1, TIGIT is an inhibitory receptor upregulated upon T cell activation. Based on this mechanism action, ociperlimab is positioned to work together with tislelizumab to augment clinical response in PD-1-sensitive tumors. ociperlimab is one of the most advanced and potent anti-TIGIT antibodies. We made a data-driven decision very early on to start our phase I combining with Tisla based on our preclinical data. With all the available data so far, that was a clear right decision, which allows to advance this program rapidly into pivotal stage to be competitive in the leading pack. To date, more than 200 patients have been treated with the ociperlimab Tisla combination. The combination is well-tolerated without additional safety signal compared to PD-1 monotherapy. We're quite comfortable with the early anti-tumor activity seen so far. Two phase III studies have been initiated earlier this year in non-small cell lung cancer. ociperlimab clinical program continues to be rapidly expanded, which I will show you in the next slide. 301 and 302 are the Two phase III studies initiated in patients with untreated locally advanced, unresectable non-small cell lung and first-line PD-L1 high non-small cell lung, respectively. Five phase II studies have started or about to start in tumor types such as non-small cell lung, small cell lung, cervical cancer, esophageal squamous carcinoma, and hepatocellular carcinoma. Lastly, BTB 90105 is our ongoing phase I/II study in a variety of tumor types. Additional settings and the indication are being further explored. Sitravatinib is a potent multi-kinase inhibitor designed to overcome immune resistance by reversing immunosuppressive tumor microenvironment. It dampens tumor-promoting angiogenesis retargeting VEGF receptor. Sitravatinib also suppresses the macrophage immunosuppressive activities by inhibiting TAM family kinases such as AXL, TYRO3 and MER. BeiGene is developing this program in collaboration with Mirati. As shown on this slide, combination for sitravatinib with a PD-1 showed promising clinical activity in several PD-1 refractory relapse tumors or PD-1 cold tumor. Based on our internal phase II data as well Mirati's phase II data in non-small cell lung cancer, a phase III study investigating the combination for sitravatinib with atezolizumab in non-small cell lung patients, including both squamous and non-squamous histology, have been initiated recently. The breadth of BeiGene solid tumor portfolio not only allows to develop a robust combination strategies and also tumor-focused strategies in multiple tumor types. Non-small cell lung is one of the examples where we have a number of phase III trials that cover a full range of the disease settings from early to late lines, treatment naive to treatment resistance. As shown on this slide, we have two ongoing phase III trials in early settings. One in new adjuvant setting, the other one in unresectable locally advanced phase III setting. In terms of first line and beyond, we have five phase III trials, among which three have read out positive at the interim, two are currently ongoing. Next program is a zanidatamab bispecific HER2 antibody that BeiGene is developing in collaboration with Zymeworks. It's designed to simultaneously bind to two distinct HER2 epitopes where trastuzumab and pertuzumab bind. This unique mechanisms action provides increased tumor cell binding and enhanced HER2 internalization compared to trastuzumab, and translated to enhancing activity across multiple HER2-expressing tumor types in the clinic. A single-arm phase II pivotal trial in second, third line HER2-positive biliary tract cancer was initiated last year. The phase III in combination with chemo tislelizumab in first-line HER2-positive gastric GE junction cancer will be initiated later this year. BGB-A445 is another truly differentiated unique OX40 agonistic antibody with distinguished mechanisms action compared to other OX40 antibodies in the clinic. As illustrated on the right of the slide, other OX40 antibodies in the clinic are ligand blocking, thus induce suboptimal OX40 signaling in T cells and also lead to loss of OX40 ligand signaling in APC cells, which translated to less optimal activity in the clinic, especially at the higher dose level, which is so-called hook effect. In contrast, BGB-A445 retains OX40 ligand signaling in APC cells while achieves maximum T cell activation because of a non-ligand blocking feature. Currently, dose escalation is ongoing for BGB-A445 as either monotherapy or in combination with atezolizumab. Safety-wise, it's quite tolerable and no DLT to date. In terms of efficacy, we're excited to see anti-tumor activities in both mono and combo cohorts. BeiGene plans to start the dose expansion phase II portion of the trial later this year or early next year. The next molecule is our potential first-in-class HPK1 inhibitor, BGB-15025. HPK1 stays downstream of TCR signaling and functions as an intracellular immune checkpoint to inhibit T cell activity. Based on its mechanism of action, we believe our HPK1 inhibitor is well-positioned to be combined with tislelizumab in PD-1-sensitive tumors. HPK1 is not an easy kinase to target due to its very low ATP Km. BGB-15025 has impressive kinase selectivity, robust activity, and a good safety profile in preclinical studies. In phase I, dose escalation is currently ongoing. Due to time limitation, I did not have a chance to cover many other programs in our solid tumor portfolio. I hope I have convinced you that we have built deep and robust clinical programs based on our science. We continue to be very focused on combination strategies with the aim to address some of the key scientific questions and unmet medical needs. For example, to PD-1 resistance. While we are extremely excited to see more assets in our portfolio entering late stage, we are equally excited about the multiple waves and molecules coming from our discovery research. I'm going to pass it over to Lai, who will lift the curtain on BeiGene's new modalities and upcoming pipeline for you. Lai. Thanks, Ben. In the first decade of BeiGene's history, all internally discovered molecules in the clinic were either traditional small molecules or monoclonal antibodies, and that we achieved many success. There are limitations associated with these traditional modalities. What we can do is often guided by what we know and the technology we have. Human beings will continue to uncover the fundamental science behind life and death. Biotechnology has evolved tremendously in the past half-century and is taking a different trajectory in its growth in the last decade. We truly believe the growth of biotechnology will propel this industry to a new high and help us to address many unmet medical needs. BeiGene has invested heavily in new technologies, which I'm going to walk you through in the great details in the next few slides. Here are the two goals we're trying to achieve with these new technologies, drugging the undruggable and precise tumor targeting. The former will help us solving many unsolved problems, while the latter will reduce systemic toxicity associated with anti-cancer medicines and improve quality of life for patients. First, let's talk about drugging the undruggable. Many targets are historically considered undruggable due to many different reasons. Lack of enzymatic activity, no suitable binding pocket, difficult to disrupt the protein-protein interactions. CDAC, or chimeric degradation activating compound, is a bivalent molecule that brings the target of interest and the ubiquitin E3 ligase into proximity that induces selective targeted ubiquitination and degradation. With this mechanism of action, CDAC can be used to hit a target that does not have enzymatic activity. Another major hurdle for traditional small molecule is to identify strong and persistent binder to a particular target. The target binding requirements for CDAC is low due to its catalytic nature. CDAC can also eliminate the scaffolding function of a target. With all these characteristics, CDAC has opened the door for medicinal chemistry to hit many targets that were previously considered undruggable. BeiGene is expanding our knowledge and building strong capability to work on novel E3 ligase, including both ubiquitously expressed and tissue-specific ones. Bottom left panel shows an example of E3 ligase with different degree of tissue specificity. By leveraging tissue-specific E3 ligase, CDAC can achieve tissue-specific target degradation, therefore reducing toxicity associated with ubiquitously targeted demolishment. Novel E3 ligase possess other favorable applications, such as overcoming E3-associated drug resistance and broadening substrate spectrum. We have multiple CDAC program ongoing, targeting various signaling pathways. Many of these are previous considered undruggable. Some of them have enzyme-independent scaffolding functions. Our CDAC platform is positioned to significantly broaden our solid tumor, hematology oncology, and immuno-oncology portfolios. Worth to mention is that many of these programs apply in tissue-selective E3 ligase system. Here, I'm excited to introduce our first CDAC program, BTK CDAC. BTK is a kinase and certainly druggable. Why do we still need to make a CDAC? BTK CDAC can overcome multiple resistant mechanisms to BTK kinase inhibitors, including cysteine-481-serine mutation reported for irreversible BTK inhibitors, as well as scaffolding function for BTK protein, which has been suggested to activate downstream BCL signaling pathway in a kinase-independent manner. We believe BTK CDAC can further strengthen our BTK franchise. BGB-16673 is a highly potent and selective BTK degrader. It has good oral bioavailability and a long half-life. It was well-tolerated in animal studies. We expect the first in-human study to be initiated in the next couple of months. As shown in the figure on the right, BGB-16673 is highly effective in inhibiting C481S mutation tumor growth. We will talk about precise tumor targeting. Tumor-associated antigen, TAA, provide a perfect means to achieve tumor-specific targeting. There are currently 10+ TAA antibodies being developed at BeiGene. These TAAs cover a broad spectrum of cancer types, including prevalent solid tumors as well as heme indications. These TAA antibodies can provide a variety of opportunities to develop precise precision tumor-targeting therapeutics via tumor-selective immune cell activation and tumor-targeted cell killing. In addition, we are also developing tumor-selective cytokine using a pro-cytokine format. I will dive into details for these different modalities. One way to achieve tumor-specific immune cell activation is pair TAA antibodies with immune cell engagers. On the TAA side, it can be either mono-specific or dual targeting. Dual TAA targeting could further enhance tumor specificity and affinity. On the immune cell side, we have multiple immune cell engager programs ongoing, including 4-1BB and the CD3 for T cells, and the CD16 for NK cells. BeiGene has built a comprehensive bispecific antibody discovery platforms to achieve diverse formats for different mechanism actions and to ensure speedy and successful delivery of drug-like molecules. This includes llama single-domain antibody screen platform, human single-domain antibody phage library, common light chain antibody, and the single chain Fv engineering platform. Another means to achieve tumor-specific immune cell activation is to use external immune cells expressing a CAR, chimeric antigen receptor, that will recognize TAA on the tumor cells. The field was pioneered by autologous CAR T therapies, but they present significant manufacturing and safety hurdles. That said, with the recent advancement on deriving allogeneic off-the-shelf and the reproducible single source sterile product, it is now possible to overcome these challenges. Recent early data on off-the-shelf CAR-NK suggests good clinical activity with much improved safety profile. Our strategy is to jumpstart with a key collaboration with Shoreline to fast-track some programs into clinic, while allow our internal capability to facilitate the partnership and the growth to expand the future pipeline. The collaboration with Shoreline and BeiGene is quite complementary, taking full advantage of Shoreline's expertise in iPSC, NK functionality, and cell therapy, and BeiGene's capability in biologics and clinical development. Portfolio-wise, we expect iPSC-derived CAR-NK will be the initial focus, but we will keep a close eye on other immune cell types with therapeutic value. TAA antibody can also be used as a missile to bring small molecules to the tumor microenvironment. This is often known as antibody-drug conjugates, ADC. We are developing ADCs with two different mode of actions. One is traditional ADC that delivers a toxin to kill tumor cells. Another mode is to bring immune stimulator to tumor microenvironments to trigger local immune activation. This is called immune stimulating antibody conjugates, ISAC. BeiGene currently has TLR7 agonist ISAC programs ongoing. BeiGene's ADC platforms aims to develop next-generation ADC designed to have superior efficacy and safety. One strategy is through collaboration with Ambrx to generate ADC with universal DAR. Ambrx platform is differentiated in its stable, site-specific conjugation technology for your precision incorporation of non-natural amino acids and has been clinical validated. Innovative linker design is another direction with the goal to utilize hydrophilic and/or masking linkers to improve ADC biophysical property and stability, and function cleavage kinetics to enable tumor-selective cleavage. Lymphocyte stimulatory cytokines have always been attractive direction to pursue in IO fields. However, the application is largely limited by on-target toxicities of systemic activation of the immune system. As illustrated in the graph on the right, pro-cytokine design is to keep cytokine in an inactive state in the circulation by a masking moiety attached to a peptide linker, which is cleaved by a tumor-specific protease in the tumor microenvironment, thus releasing the active cytokine and achieving local activation of immune cells. BeiGene's proprietary pro-cytokine design is potentially superior to some of the competitors for the following reasons. Complete masking of cytokine activity in peripheral, full recovery of its activity once cleared, extended half-life, and a plug-and-play format that can be readily applied to various cytokines of interest. Our discovery engine experienced exponential growth since 2019, not only in scale, but also in technology and platform. There are over 50 preclinical programs currently ongoing at various stage. We expect that the number of new clinical molecules per year will accelerate, with more than 10 potentially first-in-class or best-in-class projected to enter the clinic in the next 24 months. Starting from 2019, BeiGene began to invest in immunology and inflammation. Our first II molecule is expected to hit the clinic later this year. In addition, I'm very excited to share with you that we are building a BeiGene institute to focus on early technology and translational science. On this slide, I want to use immuno-oncology as an example to show you the breadth of BeiGene's portfolio. Immuno-oncology has certainly been the main focus for BeiGene. This figure laid out our current clinical commercial stage assets. I hope you can appreciate that we're developing molecules to mobilize the effector cells, as well as reshaping suppressive tumor microenvironments for multiple entry points in the immune cycle. On top of our existing assets, even without TAA-based therapeutics included here, you can see 10+ more immunomodulating programs are being developed out of BeiGene as the next wave of cancer-attacking therapeutics, such as TRAC and tumor cell depleting molecules, NKT-stimulating cytokines, as well as other novel targets to rejuvenate anti-tumor immune functions. I'm sure you would also appreciate TAA-based bispecific immune cell engagers, CAR-NKs, and ADCs will further light up the tumor microenvironment, and can be combined with many agents shown here. We have shown you a lot today because we have accomplished a lot since last year. Let me say, you are only seeing the tip of iceberg when you consider BeiGene's journey. zanubrutinib and tislelizumab demonstrate our scientists' expertise and passion, as well as the significant role we play in advancing new breakthroughs for cancer. Our strong and diverse portfolio has been built around these cornerstone assets, and many of them are now entering the pivotal stage. In addition, today's review has shown you that BeiGene's R&D model is innovative, unique, and big. Our discovery engine is continually growing and is stronger than ever, as we have the culture in our labs and the talents to do great things. The clinical pipeline is expected to quickly accelerate in the next few years. With a deep portfolio, we have a toolbox, as Xiaodong referenced earlier, to develop novel and science-based combinations. With our truly internal global clinical development capability, while we are suited to handle the quick-growing clinical portfolio at two-third of cost and two-third of time, ultimately bring innovative and affordable medicines to patients around the globe. Our journey continues, I promise much more to come. With that, I will hand it over to John for closing remarks. Thank you, Lai. Xiaodong and I laid out at the beginning our vision and our goals and the mission. It was to provide great science to impact patients, to do so affordably with more accessibility around the globe. That's been the goal. To do that, we built these strategic capabilities that we saw would be important in the future. We've talked about it. One is our global clinical development team at two-thirds the cost and two-thirds the time, improving. That is a capability that we're proud of, you've seen, and it's real. From the second perspective, we built an innovative science team. That's hard to do. Some companies are successful, it's very challenging to build that culture and that true innovation. We've been successful at doing that, too, as Lai pointed out, we've been able to do that at scale, which is always a challenge. The third competitive advantage we talked about was building distribution in China, as that was a greenfield space, becoming one of the true leaders there. I think we haven't talked about that today, it's very clear that we're incredibly well-positioned in that space. As we think about today, what have we learned over the past decade? Certainly, some things we've learned. One thing we learned along the way was it's very important to control your own manufacturing. You need it for speed and for flexibility. Another thing that we've learned is science has been even more impactful than Xiaodong and I envisioned in the last 10 years. There's so much going on that to keep up with it, you need to have deep understanding and breadth of knowledge. The third thing, it's very competitive, more competitive than anyone would have imagined. Speed is critical and important in the future. I think the last thing is it's very clear new modalities are going to play an important role. We have to follow the science, as we committed to from the beginning. That's where it takes you. What does that mean we're also trying to do to complement these first strategic capabilities we were building? Well, first of all, it's not a subject for today, but we had to build our own manufacturing capabilities so that we could act with speed, so that we would have that flexibility, so we would have cost advantages there. Simply, Xiaodong and I didn't understand that at the time, but it's clear today. It's a very important competitive advantage. The second thing, we realized we need to follow the science into the new modalities. Critically important, and that's been being done and is now being shared. The third thing that was obvious is a lot of the future is going to be around combinations. If you think of what the implications are of that, there's two. The first implication is organizations that have a broader toolbox of building blocks for combination solutions are going to have a lot of advantages. They're going to have advantages in clinical development because they can move with speed. They're going to have advantages in clinical development because they're going to have lower costs in partnering with other companies or purchasing things they need to do that clinical development. The second implication is the nature of those studies, they're going to be bigger. They're going to require more clinical characterization, more science that's being done at the clinical level, not just the preclinical level. As a result, an organization that can be more effective in cost and time clinically has a huge set of advantages in that world. As you think of how you build those, it's very important for us to have this broad toolbox, and it will be a strategic advantage in the future. I think as you've seen over time, BeOne Medicines is a company that's bold. We're a company that's persistent. We're a company that's thoughtful about what we're doing. Not only are we developing great medicines, but we're doing it in a way that's very unique. We're trying to do what's right for patients all around the globe. With that, I would like to thank you for your listening today, and I'll hand over to Gabrielle for our questions and answers. Thank you, John. With that, we conclude our prepared remarks. For our Q&A session, the speakers will be joined by our senior leaders you see pictured here. Julia Wang, our Chief Financial Officer, will moderate the Q&A. As a reminder, to ask a question, you will need to be joined to this call using the Zoom application on a computer or a mobile device so that you can access the Raise Hand feature. If your audio connection to the call is by phone, please be sure you've joined through the Zoom application first and then enter your participant ID. This will enable us to unmute your line. Please note you will need to permit your line to be unmuted before you begin to speak. Your Zoom profile should include your full name, and please state your affiliation before asking a question. There will be a brief pause now while we assemble the queue. Our first question comes from the line of Andrew Behrens. Please go ahead. Hi. Thanks for taking the question, and thanks for hosting this event. Just because I wanted to get a little more color on the BCL-2 program, four one seven, what type of resistance are you hoping to target with your drug? Then also you mentioned you hope to have a profile similar in terms of safety tolerability to Xano in the BTK market, but what specifically are you hoping to improve upon versus venetoclax? Thank you. Hi, Andy. Thank you for the question. Hey, Lai, can you please respond to this question regarding BCL-2? Sure. Thank you so much, Andy, for the question. In terms for our BGB-11417, as Bill illustrated, this molecule has better selectivity as well as better potency compared to venetoclax. We actually believe the tolerance will be very similar to what we have been telling you about our BTK inhibitor compared to ibrutinib. Also, as Bill mentioned, at this moment, the clinic will already reach the 320 milligram QD daily dosing. We actually observed the PK at 80 milligram, similar to ibrutinib, venetoclax PK exposure at its clinical dose in CR at 400 milligram. If you think about it, we are probably about fourfold higher exposure now already compared to venetoclax. That's quite impressive. In some of the resistance, venetoclax has reported several resistance in using CLL, including G101V. This molecule, one one four one seven, can indeed hit G101V mutations. In addition to that, I can tell you we actually have another BCL-2 molecule in our pipeline, which can probably hit the G101V even harder, and also includes some of the other BCL-2 mutation has emerged with the venetoclax. I think the question you have also is about what's the kind of clinical development plan and how are we going to move this forward. We're still in the dose escalation, and we are very excited about what we have seen so far. So far, the activity as well as safety is on par with what we should have already predicted based on the preclinical data. The goal, certainly one of the key space, is combination with BTK in the CLL. Beside that, we do believe there's multiple application for BCL-2 outside of the CLL. Including other B-cell malignancies such as mantle cell lymphoma, DLBCL, as well as you can get into the AML, MDS, and also multiple myeloma. Also, there has been report about BCL-2 can potentially play a role in solid tumor. If you think about it, for a medicine to get into solid tumor, usually you require high exposure, because oftentimes, the drug concentration in tumor is lower compared to in the plasma. If we can indeed achieve a high exposure in the plasma, we actually probably have better chance to hit BCL-2 in the solid tumor. We are indeed developing a broader program around our BCL-2 to be combined with our BTK, as well as get into other disease settings. Thank you for all the color. Appreciate it. Thank you, Andy. Our next question comes from the line of Eve Raleigh. Please go ahead. Hi, it's Yaron Werber. I'm not sure if you can hear me. Yes, we can hear you. We can hear. Okay, great. Thank you so much. I have a couple of questions. The first one is on sitravatinib. It looks like you're now moving into a pivotal study in PD-1 refractory patients, in combination with this. It's going to be in second or third line. How is that study different than the Mirati study that's going on, that's going to yield data late next year? Then secondly, on the Seagen collaboration, it looks like this is the first time, at least that I've seen, that it looks like it's targeting CD70, I assume it's an ADC compound. Crizotuzumab from JNJ and argenx showed really solid data as monotherapy, but when they went into first line in combination with venetoclax and VITEZZA, JNJ returned and writes, "We think the efficacy was there, but it looks like it was probably a narrow therapeutic window." Maybe just comments of how you think you differentiate it, and what's your plan to develop it. Thank you. Thank you, Yaron. On the first question regarding sitra, Ben, could you please provide your comment? The second question regarding the Seagen CD70, Lai, could you please share a bit of your thought? I probably can take the first one. I'll probably defer the second one to Leo or Lai, if that's okay. Yeah. There are two main differences regarding our study design versus Mirati's phase III SAPPHIRE study. The phase III we are sponsoring is including both squamous and non-squamous, versus only adenoid in the SAPPHIRE study. The second difference, the combination in terms of PD-1, apparently our study is combining with Tisla. The SAPPHIRE study combines with nivolumab. Yeah. Relates to the CD70. This is a program we're collaborating with Seattle Genetics. It's ADCC-enhanced version. This molecule is still in the phase I dose escalation phase. We have the Asia. I think it's Asia ex-Japan, plus Australia and New Zealand, right? That's the current status. I can tell you, early data looks quite promising. Great. Thanks so much. You're welcome. Thank you, Yaron. Our next question comes from Zhengzhuo Li. Please go ahead. Thank you for taking my question. I just want to ask a little bit more about the new modality Lai has talked about. I want to understand a little bit about the strategy or rationale behind it when we are looking for a new modality to develop. How do we think about different areas to get into? Among those new modalities, which one are we most excited about, and when we can expect some clinical data? Thank you, Lisa. Lai, please take the- I'll probably take that question. Thanks for the question. As I highlighted earlier, I think that one of the key things-- There's two things we're really looking forward to have the new modality help us to address. One is potentially be able to hit on targets previously was considered undruggable. The second part of it is we do believe, with the evolvement of the new technology, you want to be more specific. Here, we'll talk about being more tumor specific. Many of our new modality is around can have a precision tumor delivery of the particular therapeutics. In terms of drug undruggable, we certainly believe the CDAC platform provides the opportunity to work on many targets which were previously really looking forward to work on. In terms, the question relates to which one I'm most excited about. I'm excited about all of them. We have so many different programs we are cooking. You have seen a little sneak peek of what we show you today is our first CDAC program. That's a BTK CDAC. If you talk on new modality, that's probably the one you will be able to see the data, the quickest. The data to show up for that molecule is probably going to be relatively quick. Maybe I just want to add one more point about while we're working on the BTK CDAC. I do believe that BTK resistance is way more than just the cysteine mutations. From our own study with our zanubrutinib in the clinic, we have observed additional mutations which seems like it's function as a scaffold function. With the BTK inhibitor, you cannot remove the traditional BTK kinase inhibitor, you cannot remove those scaffold function. The BTK protea of CDAC will be able to degrade, remove the BTK protein, therefore diminishing those scaffolding functions. I think that would be very exciting. Behind that, you're going to see a whole bunch of other new modalities getting to connect in the next one or two years. Thank you. Maybe just a quick follow-up. On the new modalities, how do we think about the mRNA platform and also maybe some gene therapies? Do we have interest in those area, and how do we think about our strategy developing those area? Actually, in half the slide we have about our preclinical pipeline, there is a symbol stand for mRNA. We're definitely investing into the mRNA. It's just today due to the time limitation, didn't get chance to talk about it. Certainly, there has been tremendous interest in mRNA, like what we have done in the past, we don't want to simply just dive into technology because it's hot. We want to make sure we have the knowledge, understanding, and the know-how to differentiate. In BeiGene, even though CAR T was extremely hot for already probably close to a decade now, we never really invested in CAR T, especially the autologous CAR T. We didn't feel like that was a way to be able to make medicine with enough safety and also the cost advantage. In term of mRNA, certainly, there's a lot of interest. In gene therapy, we haven't started on that part yet, we're looking into that. In addition to mRNA gene therapy, we're also looking into many other different therapeutic modalities. We'll keep our eye open. As I mentioned, I truly believe biotechnology is now going through a transformative era. If you're not following the technology, you could easily be left behind. Great. Thank you for the color. Thank you. Our next question comes from Matthew Harrison. Please go ahead. Great. Appreciate you doing this. I was just wondering if you could comment more on the HER2 molecule and what you see as sort of the path to registration for that molecule, and how we should be focused on maybe some upcoming data sets for that. Thank you, Matthew. Hey, Ben, do you want to get us started on this one? Sure. As I briefly mentioned, there are two pivotal trials. One has started, in second, third line biliary tract last year. We are expecting the data hopefully in the near future. The second one is the first-line gastric, in combination with the tisla and first-line chemo. That's about to start later this year in collaboration with Zymeworks. Yeah, Matthew, did I answer your question? You did. Thank you very much. Sure. Thanks. The next question comes from Michael Schmidt. Please go ahead. Hey, guys. Thanks for taking my question. I had two bigger picture question, as obviously I'm very impressive to see the tremendous growth the company underwent, which looks like potentially accelerated the last couple of years since 2019, as you mentioned. You're now on a $2.8 billion annual run rate for operating expenses. How should we think about the rate of OpEx growth over the next few years? Is it anticipated to reach a plateau at some point, or do you expect to continue to grow at the current rate? That's my first question. Then the second question is really on your global commercialization strategy. I was just wondering how you're thinking about partnering or out-licensing commercialization rights outside of Asia like you've done with tislelizumab versus globalizing some of these innovative agents in-house on a global basis. Thanks so much. Thank you, Michael, for the questions. The first one regarding the OpEx, maybe I can provide a bit of a color. In terms of the investment, if you were to break down the areas of strategic importance to us, of course, today, as we are talking about here, is the research and development side. If you think about research and development, as Lai shared, from a research perspective, we do expect to continue to invest in order to strengthen our competitive advantage. With that being said, as you can imagine, as John articulated earlier, if we look at the cost overall for our industry, the majority of the cost is upfront. It is really in development. Even though research is increasing, we do expect that to continue to be a smaller component of the overall R&D investment. From a development perspective, obviously, on the one hand, we just have some of the trials for assets that have already reached the commercial side, whether it is tislelizumab or zanubrutinib. You can imagine that the trial cost associated with those assets will start ramping down a bit from a curve perspective. At the same time, as we move more new assets through the clinics, whether it is advancing TJ into the clinical stage or hopefully DFL2 into the clinical stage, it would start taking up a bit more investment. Overall, from a clinical standpoint, you can continue to expect us to invest at a level that is consistent with the portfolio evolution. Of course, we continue to build strategic capabilities as we internalize the clinical development around the world. You can also expect a level of investment in that regard. Outside R&D, if you look at our strategic imperatives, one of them is really maintaining the leadership from a commercial perspective in China in particular, that is science-based, of course. As we continue to leverage the commercial assets in our portfolio and capitalize on the NRDL implementation, we do have plan to continue to stay true to building one of the very competitive commercial capability in China and certainly around the world. All in all, from an investment perspective, I would say we wanted to ensure that we judiciously allocate in a way that would enable us to stay on track of maintaining a competitive advantage over time that would lead us to become a leading global biotech company. With that being said, we are deeply sensitive to the consideration that as we continue to grow, it is equally important that we maintain the balance between speed, agility, and efficiency and productivity. In that regard, we have done a lot of work internally, whether it is process, it is system, or it is capability, to ensure that we institute a rigor of productivity mindset as well as scorecard and metrics to ensure that there is transparency on how we manage our investment. There is also transparency in how we hold ourselves accountable for return on investment. Your second question is regarding the commercial strategy, partnering, out-licensing. I think we have Angus, our Chief Business Executive, on the line. Angus, can you please take that question? Yes. Obviously, we have a very active business development team. We look at a number of opportunities for in-licensing assets that either give us access to the marketplaces in China, the U.S., and Europe, and around the world. We do deals that bring innovation into the company, such as the one that Lai referenced, the Shoreline collaboration. Then when it comes to out-licensing, it's always a question of does it bring additional sort of support resource or expand the potential of us to do the best for our drugs, such as the collaboration we framed with Novartis for tislelizumab. We really have an active business development team that looks at all fronts. Obviously, it would be inappropriate for me to tell you about the deals we have in the works. Thank you. I might throw in to that answer that over time, our long-term intention, of course, is to have our own oncology commercial resources in North America and in Europe in solid tumor. We've made that clear. I think we very clearly knew that for the PD-1, the best way to get that asset to patients and to form the most combinations with it as possible was a deal with Novartis. I think over time, as we become stronger and stronger in these areas, there will be a natural point at which we can and will do everything ourselves. At the same point in time, I think we're not quite at that line, and we're building towards that line, and it's really going to be situation specific, but I think that we're very confident in the capabilities of our U.S. commercial team, and we're very confident in the capabilities of the team that's being built now in Europe. I think that it would not be surprising to see many of the things that Lai's talking about commercialized by our company directly in those markets. Thanks, John. Thank you. Our next question comes from the line of Yang Huang. Please go ahead. Thanks. I have two questions. My first question is probably for John. I understand to have our own clinical development team does have a lot of advantage. However, it seems very unique that not many pharma or biotech companies build its own clinical team without relying on outside the CRO companies. My first question is, what kind of advantage does BeiGene have to allow us to implement such a unique clinical strategy? My second question is probably about how to balance our development or commercialization in China and ex-China. Let's say, what should we think about in five or 10 years in terms of our sales, how much will come from China and how much will come from ex-China? Thanks. Sure. Thank you for the question. I think for starters, as we talk about building our own clinical organization and what that means from a capability perspective, everyone in the industry wants to be doing cutting edge sexy science. Everyone in the industry wants to have commercialization and revenue. Those are things people get excited about. To be honest, clinical trial work is hard. To be honest, a lot of it that's outsourced to these third parties, it's not glamorous. It's hard. There's people that are attention to detail, that are doing a lot of things where they don't necessarily get the glory. They're probably not always as appreciated as they should be in our industry. This is the heart. It's the heart. It's 75% of the cost. It's over 75% of the time in doing this well. To me, I don't understand why every company in the industry doesn't say, "My core competency has to be being the best company in the world at this." It is very recognized. I said a polite sentence somewhere in my talk, but it's well recognized by everyone in the industry that the net result of the way the industry's evolved is highly inefficient clinical trials that take a long time, that cost a lot, and that haven't adapted to operational excellence nor implemented the latest technology. I think for small companies, it's easy to understand. For small companies, you don't have the breadth to be able to do it. You really need to have a broad pipeline to be able to justify making the investment in building this type of an organization yourself. If you're going to build it has to be really high quality because you can't have quality mistakes. These are critical. The third point, which is a little left off of what we described, is a lot of the places you need to go to get the next clinical centers into the system, a lot of the CROs aren't operating there. If they are, they have limited resources that aren't sufficient for the amount of clinical trials that you'd hope to do there. I think this is the thing that needs to change in our industry, period, if we want to make innovative medicines quickly to patients. I think BeiGene is the only company I know saying we want to be the best clinical development organization in the world. We're the only one building an organization fit to that purpose and really committed to doing it. Yes, I think it is unique. The second thing around it is, it's hard. We didn't do it overnight. It's really hard to build this type of an organization. It's global. It's not just in China, it's not just in Australia, it's not just in Europe. It's a global team. Getting a global team to work together, it's hard. There's a lot of systems and there's a lot of technology software that needs to be invested. There's a lot of SOPs that have to be in place to be able to do it from an appropriate perspective, something that's really hard to build, and we've done that. Some of the pharmaceutical companies have done it too, but they probably don't have the global reach we have, and they're probably not doing as large of a percentage of the work in-house. There's investment to set it up. The payback, this is the best investment you can ever make. The payback is lower cost and speed advantage when you run clinical trials. We would have a larger team if we could build a larger team with deeper capabilities in this area because this is the one investment we know there's a surefire return on. It's the one strategic capability that is truly unique to BeiGene, and it's something that has already had tremendous impact to our company. If you look at our PD-1, for example, our PD-1 has generated very substantial cash payments from third parties in partnering it. This is because our PD-1 has a global data set that's one of the biggest global data sets in the world for a PD-1. It's not as big as KEYTRUDA or BMS's, but the clinical data set we have outside of China is tremendous. I don't have the exact numbers, Lai, could share that, but it's well over 1,000 patients. That's unique. Other companies don't have that. That's why you see the type of deals that we've done. The breadth of that program, the thousands of patients on it, we've been able to do that and execute and afford to do it because we have this internal team ourselves. I think this is, as Lai said, the tip of the iceberg. This is a critical, valuable core strategic capability. We'll continue to invest in that. It's very clear. Why haven't other people done it? If you're too small, you can't afford the investment. The other reason is, it's really hard. Great people don't want to come and join a team unless they believe in the science you're doing. They don't want to work on a B worse asset. They don't want to work on a very small pipeline. They want to come and join something that's truly exciting. You talk about what we're doing clinically, this is probably the most exciting place in the world to work if you're in clinical development because we're so committed to it. I think that's why we've been able to be successful in this area. It's the vision of the importance of it. It's the commitment, and I think it's a great place for people to work that are in that area of our industry. I'm sorry, I think I probably forgot your second question. My apologies. Sure. The second question is about the sales compensation globally and the sources of growth in different geographies over time. In terms of answering that question, we don't see the world as China and non-China or China and the U.S. and everywhere else. Global development, if you're spending the investment to do great science, make an impactful medicine, your market by definition is the world. I would encourage all investors to think about it that way. We have been asked over the last three years, why do you spend more to invest outside of China? We spend 20% more on programs to make sure that we can be approved globally, but only 24% of the cancer patients in the world are in China. Clearly, the price point in China is going to be much lower than that of the United States and Europe. With that said, if you're making that incremental investment, the payback's huge. It's huge. To us, there is only a global market. I think that you will see over time that companies that focus on the traditional one-sixth of the world will have a big problem because you've got to be very successful in China. It's where 24% of the cancer patients are. It's at least the second-biggest oncology market in the world. I think you'll see if you only focus on China, you're probably only in a third or a quarter of the global revenue, and your competitors are in the total global revenue. There's only a global strategy in the future. How's that going to play out for BeiGene? It's going to depend how the world evolves. We probably think U.S. pricing is going to change and be more affordable, and that's okay. We probably think that China pricing is largely where we had expected it to be, and it may go up and it may go down over time as we try to sort out the equilibrium. In the long run, clearly, there's a desire to have an innovative, profitable industry in China. That's the goal of the country. I think in the long run, you're going to see different perspectives. However it is laid out, though, BeiGene expects its revenue in the long run to be split evenly based on the way oncology medicine is distributed across the world. We clearly expect to be one of the major providers and the most impactful company in China. I think that over time, we expect to be a major player, perhaps with a smaller market share, but a major player across the world in the other markets. Our expectations is for global revenue where China is substantial, but it's not even clear that's a majority over time. Great. Thanks a lot, John. Sure. Thank you. Our next question comes from Chan Hur. Please go ahead. Thank you for taking my question. I probably have a few. I will go one by one, so it's easier for everybody. I guess the first question is probably to Ly or Ben. Can you comment a bit on what's your anti-TIGIT development strategy versus the other first pack movers like Roche or Merck? I hear somebody saying our anti-TIGIT program is a bit too aggressive. How would you comment on this? Ben? I refer this to Ben. Ben? Maybe I can start. As I mentioned earlier, we have two phase III studies currently ongoing in non-small cell lung. For multiple reasons. Number 1, we have a tumor-focused strategy. Lung certainly is one of the top tumor types we had to focus based on the portfolio we have, also the clear and medical need. We took a calculated risk based on external proof of concept data. That's how, nowadays, with the new therapy promise, we move more quickly than ever before. That's the decision we made based on external data, which actually is quite appealing in non-small cell lung space. In terms of differentiation, we talked about this previously. We believe, at least based on the data available, not just from our internal clinical studies and also external studies, I think the IC function may play a role in the context of TIGIT. This is probably the most potent TIGIT antibody with the right IC function. The clinical data will further confirm whether that's true or not. With all the data in hand, we think we're quite competitive, at least in the initial tumor types. In addition to the phase IIIs, we continue to generate the proof of concept data in other tumor types. Based on the data from those studies, we'll make a data-driven decision again for additional opportunities for late stage. Lai, do you have anything to add? Angus, you covered that well. Okay. Yeah. Julia, I'd add, it's fair to say that this is a riskier proposition than many things we do. At the same time, the return is an order of magnitude greater than many things we do. We always assess, is this a risk we're willing to take and is the return there? I think in this instance, the risk-return is there. Unquestionably, you are correct. It's riskier than the average thing we do. The reason we've chosen to do it is the return is much, much, much greater than the typical things that we do. There's a calculated risk there, no question. Good. Thank you for that. I think the second question is regarding the PD-1 sitravatinib. I think in China, the PD-1 population, especially the resistant, will be big. Is there going to be any proof of concept data that to help us gain a better understanding of the chance of success for the phase III, in a pretty large indication in NSCLC for the PD-1 plus sitravatinib combination? Hey, Ben, can you please respond? Yeah. Happy to. I first mentioned the decision was based on two sets of data. One from Mirati Therapeutics, phase II study. The medium OS holds up nicely after long period follow-up. That data is available. In addition to that, we also run phase II trial in both non-squamous and squamous. I think we're going to share more mature data at upcoming ESMO. It's quite consistent with the findings in the Mirati Therapeutics study. Based on two phase II trials, the decision was made to go into phase III including both squamous and non-squamous, again, in addition to the adenocarcinoma histology included in the SAPPHIRE Mirati Therapeutics-sponsored study. That will cover a wider population, if you will. Cool, we should Yeah, go ahead. Sorry. Sorry. Maybe I just add one comment. I think this is really, as Ben said, we made a decision based on the data we have seen in the phase I, II we have run. I just want to add, this is more than just non-small cell lung cancer. We're seeing this activity across different tumor types. Clearly, this is due to its mechanism action, right? We're actually very excited about this mechanism action. As you pointed out, PD-1 is amazing, but there are a lot of patients who fail PD-1. We do believe if the mechanism action is true, it probably can go beyond non-small cell lung cancer. Cool. We should be very looking forward to the upcoming ESMO data then. Going back to BCL-2. For the solid tumor, when are we going to see some proof of concept data? Or it's just mostly going to be hematology indications? Yeah. Maybe I can take that question. For the BCL-2, there has been early data in the breast cancer with the ER-positive breast cancer, and venetoclax has been running few study there, either as possible in combinations with ER antagonist or with the CDK. They step back, they reported data which they did not see what they were original expected. At this moment, we are contemplating what will be the best combination partner for our BCL-2 test in the solid tumor. That's including, but not limit to, the breast cancer. We actually also think about some other tumor types, such as small cell lung cancer. There are preclinical data suggesting BCL-2 also play a critical role there. There's quite a bit since we're doing exploration. Hopefully, maybe, probably will be early next year or so, we will have our solid tumor strategy really come out and be able to escalate. Okay. I guess the last question will be a bit relevant to commercial. I mean, John, I hear your emphasis on BeiGene thesis is we do this China-rooted R&D, therefore our trial program is faster. I guess as you said, commercialization is also quite key. I guess we always eye on BTK inhibitor because now we have the best-in-class profile and we are doing this in-house commercially. Yeah, I just want to hear a bit of the team's thinking on when and how are we going to achieve this best-in-class commercial status as well. The second question is regarding China. Healthcare is a policy guided, regulated industry. Based on what has been happening in other industry, there are always concerns about what's going to happen in China. We have larger exposure to China than the other multinational companies. I want to hear the management's view on this as well. Sure. I think your first question is about commercial success at BTK and when it will look like best in class commercially. I'm welcome to invite you to our sales meeting to nag Josh at any moment, I think maybe we'll let him answer that question. I ask him that probably six times a day. Josh, why don't you answer? Sure. More than happy to. Shandy, thank you for the question. I think, if you take a step back and sort of consider the totality of the data that we now have to support particular commercialization efforts, we really believe, to a point, that we're going to be able to credibly position as a best-in-class molecule. As you look at the overall market and our positioning to date, I think we're all aware that in the U.S., as an example, our initial indication was in relapse/refractory mantle cell lymphoma, I've been really pleased with our success to date, launching in a really competitive market with the single-arm trials, and sort of being able to drive meaningful use within that indication. We're on the cusp of two potential new indications in both Waldenstrom's and marginal zone lymphoma, which we believe will position us from the other next generation BTK inhibitor by providing indications that they don't have. Then of course, to really access the majority of the market, we need to get to the CLL indications. If you look at the data that's been presented from ALPINE, that compares very favorably to the other BTK inhibitors, we're looking forward to presenting the results of SEQUOIA at an upcoming meeting as well. Right now, the key for us is to drive that initial good experience and then bridge to these other indications when the moment comes. As you saw from the clinical overview today, we have some really important points that clinicians and patients really appreciate, as compared to the other BTK inhibitors, which can be dosed once daily or twice daily, which can be given concomitantly with other agents that the other BTK inhibitors cannot, like protein pump inhibitors, et cetera. Most importantly, we're the only BTK inhibitor to date to demonstrate an efficacy at advantage over ibrutinib in any trial. That's of course based off the ALPINE trial from its priority analysis for overall response rate. The landmark analysis for PFS was very encouraging, we await the results of the final analysis there. At the end of the day, it comes down to the data positioning us to compete well, then it comes down to the team. The team that we already have in place in the U.S. is very strong. The team that we're building in Europe is incredibly strong as well, with deep experience in hematology. I think for us now, it's just a race to get to those indications and then to be able to drive more share. Hopefully that addresses your question and happy to provide any additional context. That's great. Thank you, Josh. Thank you. John, are you on mute? I think the second half of your question was given our deep presence in China, how do we feel about geopolitical tension and recent regulatory things that have occurred in China? I think that, look, I don't think we feel for our industry we're in a different bucket than we've been. I think this is an industry that if you look objectively at what's happened over the last five years, the reforms are all incredibly positive. Incredibly positive. The criticism is prices are lower in China than they are in the U.S. Maybe they're too much lower. The fundamental reality with that is, China regulators' goal is not to protect U.S. pricing. It's to do what's best for patients in China. Fundamentally, as we look economically from a global perspective, we think the price levels in China are fine. They work from a global perspective. We don't see that as an issue, we don't see regulators having a desire to drive the industry into lack of profitability. I think there's always a nervousness this time of year with investors as you're going into the NRDL, with this fear that the real desire in China is to take away all profitability and destroy the industry. I think we've actually never seen that happen. It's understandable people get nervous, I don't think that's what happened. I think PD-1 pricing has been lower and more competitive, I don't think that was driven by regulators. I think that was driven by the behavior of companies, I think it's a uniquely large asset class and you have new companies from that perspective. Our view is, of course, there's going to be a nervousness about pricing. That happens every year this time. That still exists. That always has existed. We don't believe the fundamental underlying desires are to act in a way that creates a problem for the industry. From the bigger geopolitical, we just don't see any sign that our industry is an industry that's being targeted, we think that there's a clear understanding that if your goal, which I really believe China's goal is probably more than most countries, because they have 24% of the cancer new instances in the world, is to provide low cost, impactful, innovative medicine to your patients, which is completely the entire policy that's happened the last five years. It's very hard for you to do things that step in the way of that. Again, the cost is driven by your ability to have a global market. The cost is driven by your ability to work globally on research and on clinical development. That's why Xiaodong and I believed you could get to one sixth of the cost per patient. It's implicit in working together globally. I think that people understand this more and more. We just do not anticipate that given the importance of fighting cancer with the best medicines affordably and quickly, China would pursue anything from a regulatory perspective that got in the way of that. We haven't heard anything to that degree. Thank you. Great. Thank you all very much. That's all from me. Thank you. Thank you, Shen. With this, we are wrapping up our Q&A. At this point, I would like to turn over to John to help us conclude today's session. John? Yeah. I just want to thank everyone for their time and for attending. We're only really talking about R&D, and I know there's a lot to digest. That's the incredible thing about BeOne Medicines. There's a lot going on here, but it's thoughtful. It's all in the goal of doing our best science to create impact for patients and to do that in an affordable and accessible way so we can get medicines to billions more patients around the world. The industry is global by nature. We're a bold company, we're persistent, and we're going to do what's right for patients. Thank you all, and have a wonderful day.