Good day, everyone. Welcome to BeiGene's Q4 and full year 2024 earnings call webcast. All lines have been placed on mute to prevent any background noise. After the speakers' remarks, there will be a question and answer session. At this time, I would like to turn the call over to the company. Good morning and welcome. Thanks for joining us today. I'm Dan Maller, Head of Investor Relations at BeiGene. Before we begin, please note that you can find additional materials, including a replay of today's webcast and presentation, on the Investor Relations section of our website, ir.beigene.com. I would like to remind all participants that during this call, we may make forward-looking statements regarding, among other things, the company's future prospects and business strategy. Actual results may differ materially from those indicated in the forward-looking statements as a result of various factors, including those risks discussed in our most recent periodic report filed with the SEC. Please also carefully review the forward-looking statements disclaimer in the slide deck that accompanies this presentation. Reconciliations between GAAP and non-GAAP financial measures discussed on this call are provided in the appendix to our presentation, which is posted to our Investor Relations website along with our earnings release. All information in this presentation is as of the date of this presentation, and we undertake no duty to update such information unless required by law. Now turning to today's call, as outlined on slide three, John Oyler, our Co-founder, Chairman, and CEO, will provide opening remarks and an update on our hematology franchise. Matt Shaulis, our General Manager of North America, will provide an update on the U.S. commercial performance of Brukinza. Lai Wang, our Global Head of R&D, will discuss our R&D and pipeline progress, and Aaron Rosenberg, our CFO, will review the fourth quarter financial results and our 2025 financial guidance. We will then open the call to questions. I'll now pass the call over to John. Thank you, Dan, and good morning, everyone. 2024 was a truly remarkable year in which we achieved $3.8 billion in revenue for the full year, $1.1 billion in Q4, positive quarterly cash flow from operations, BTKI leadership in new patient starts across all lines and all indications in the U.S., and Brukinza U.S. revenue exceeded Calquence for the first time in the fourth quarter. We introduced 13 new molecular entities into the clinic, and we matured as a global company with the completion of our $800 million U.S. flagship manufacturing facility, our ticker change to ONC, and our proposed name change to BeOne and re-domiciliation to Switzerland. We believe that we've reached an inflection point, and we're truly excited for the future. Our company was purpose-built to address the long-lived challenges of return on investment in our industry. As you know, it's not getting any easier to generate ROI on each R&D dollar. Clinical trials represent more than 75% of the total cost to develop and commercialize an oncology medicine, and they're now estimated to be $250,000-$300,000 per patient, still rising. It's increasingly challenging out there, but we built BeiGene from inception for a world that envisioned these challenges. Our truly global, CRO-free clinical team of nearly 3,700 allows us to move at a greater speed and a lower cost than our industry peers. Paired with our internal research and internal manufacturing, we've enabled a fast-to-proof-of-concept approach that shaves meaningful time from early-stage development. We're innovating with intentionality, and we're building best-in-class franchises with better outcomes for patients that will provide superior returns in the increasingly competitive commercial landscape. In CLL, we believe we're in the middle of a once-in-a-lifetime opportunity, which is akin to that of Gilead in HIV and Vertex in cystic fibrosis. Our focus for 2025 is to deliver upon three strategic pillars. First, solidify and deepen our hematology franchise leadership. Second, advance our pipeline of internally developed assets. Third, drive superior financial performance. My section today will focus on our heme franchise. Of course, we can't talk about the franchise and our heme leadership without starting with Brukinza. Brukinza was designed from inception to provide 24/7 inhibition of BTK in all disease compartments and to address efficacy and tox challenges of ibrutinib. As you can see here, only Brukinza maintains serum exposures well above its IC50, whereas ibrutinib and Acala exposures are well below their IC50 for the majority of the period. You can't fight cancer part-time or only in the blood. A recent peer-reviewed publication analyzed the differences in BTK occupancy between the three approved covalent BTK inhibitors. These results indicate to us that with regard to target engagement, only Zanu provides complete and sustained inhibition of BTK across all relevant disease compartments, and that Zanu is greater than ibrutinib, which is greater than Acala. These data and the clinical results shown here proved our hypothesis was correct. In the ALPINE trial, BRUKINZA demonstrated sustained superior PFS efficacy and lower cardiac tox head-to-head against ibrutinib. On the left, the ALPINE data in the high-risk deletion 17p, p53 subpopulation is shown. At 42 months, milestone PFS was 59% for Zanu and only 32% for ibrutinib. On the right is the ELEVATE- RR study, also in the high-risk deletion 17p, p53 patients, which is said to have a hazard ratio of one. But please note the early separation is likely due to lack of tolerance to ibrutinib. But more importantly, that Acala crosses at just over 30 months and actually becomes 8% worse than ibrutinib at 42 months. And at this time period, the milestone PFS is only 28%. Yes, I said 28%. And this compelling data has led to exponential growth in Brukinza global sales, less than two years from our first approval in CLL. And despite being the third to market, Brukinza has become the BTKI class leader for new patient starts. Perhaps the combination of the aforementioned data and real-world experience are leading to both patients and clinicians understanding that on efficacy, Z is greater than I, which is greater than A. I'd like to take a few moments to talk about the fixed-duration treatment landscape and why we view it as a key opportunity to grow our CLL leadership. To create compelling fixed-duration therapy, three key attributes are required. First, deep response. Second, impressive and sustained PFS compared to continuous therapy. And third, safety during the treatment period that adds only minimal liability over a continuous Brukinza, which has consistently demonstrated a favorable safety profile. Recent data presented by competitive treatment options certainly leave a lot to be desired. First, AMPLIFY did not show a deep MRD response. Actually, only 34% of AV patients reached MRD negativity, which was both statistically inferior to chemo and also dramatically worse than precedent data from similar phase three trials of VO and VI. By comparison, our combination of Brukinza plus Sonro has shown 91% MRD in a much less healthy all-comers population. Secondly, current fixed-duration options do not show a sustained PFS benefit that matches continuous use Brukinza, particularly with longer follow-up. AMPLIFY enrolled a highly selected, young, and fit population. The population represents less than 25% of real-world CLL patients. So how did AV compare to the precedent similarly fit VO data? It's simply much worse. How did A compare to I when they each combined with V? The A combination was worse in both MRD and in PFS, despite being in a fit population versus VI's unfit population. Numerically, in combination, I was greater than A, which is consistent with all the previous data. And this is even more striking as one expects fit to do better than unfit. How much better might one expect? For VO, the data is right here. Recognizing the limitations of cross-trial analyses, there appears to be a 6% to 7% improvement in PFS benefit when comparing fit versus unfit. The underwhelming efficacy of Amplify becomes even more evident when reviewing the actual PFS curves at the early 36-month period. Note Brukinza in the unfit population at 84% and A plus V in fit patients at only 76.5%. Also notice AV shows further deterioration around that time point. And finally, current fixed-duration options have a challenging safety profile during the first 60-week treatment period compared to Brukinza. And that's comparing again unfit to a highly selected healthy population. As you can see, there's a substantial additional tox burden placed on these elderly patients during the first 60 weeks, all for an inferior 36-month PFS. It raises the question for AV: is the juice worth the squeeze? We strongly believe in the promise of fixed duration, but unfortunately, the current options don't fulfill this promise. This provides a significant opportunity for a best-in-class combination of Sonro and Xdu that checks all the boxes: deep MRD responses, impressive and sustained PFS curves at 19 months, and acceptable safety. This combination has the potential to render the competitive molecules as not credible substitutes. Our phase 3 pivotal CELESTIAL CLL trial has completed enrollment against V plus O, not against chemo, and V plus O is actually a relevant and widely used standard of care. We also have ongoing phase 2 studies with early registrational potential in CLL, Waldenstrom, and MCL, and we're planning to initiate two additional phase 3 trials in CLL and MCL in the first half of this year. Another big heme opportunity is our BTK CDAC. This program has enrolled more than 500 patients and is by far the most advanced BTK degrader. We presented compelling early efficacy and safety data in a heavily pretreated population at ASH. As you can see here on the slide, the evolution of our data relative to Pirto, together with KOL feedback, gave us confidence to initiate a head-to-head phase three trial against Pirto in the second line later this year. We also have an ongoing phase two expansion trial in relapsed refractory CLL that's potentially registration-enabling and have aggressive development plans for earlier lines of therapy, including combinations. We are really excited about this program. In summary, our heme franchise is poised to win. As we are the only company with the wholly owned potential best-in-class molecules across the most important targets and modalities, we believe that we can dramatically improve the standard of care across all lines in CLL. We have a once-in-a-lifetime opportunity to build life-changing combinations and the preeminent franchise in the $12 billion-plus CLL market, and we believe our franchise model will help insulate us from pricing pressures. And with that, I'll pass it over to Matt. Thanks, John. Moving to Brukinza's U.S. performance. Brukinza's commercial adoption has been remarkable and consistent with what you would expect to see with a clearly differentiated and best-in-class medicine. Within the BTK market, we continue to strengthen Brukinza's position as the BTK of choice, as demonstrated by its leadership in both frontline and relapsed refractory CLL new patient starts. Overall, CLL new patient share has grown to over 50%, and our strength and leadership extends beyond CLL. Our new patient share is even higher across our other approved indications. New patient share is a leading indicator of value share, and we see the leadership in CLL and our other approved indications playing out on this slide. In Q4, we had $616 million of U.S. sales, representing 97% growth compared to the prior year. This solid performance capped off a strong 2024, where we had $1.95 billion of revenue, representing growth of 106% versus 2023. We surpassed Calquence's U.S. revenue in Q4, and we are close to overtaking Imbruvica, remarkably less than two years from Brukinza's CLL approval. This is testament to Brukinza's differentiated profile and our strong clinical development, medical, and commercial execution. The CLL landscape remains competitive, but we are in an excellent position as we enter 2025. The overall global B-cell malignancy market opportunity in our approved indications is large and growing, totaling approximately $21 billion in 2024. The U.S. represents a significant portion of the global market, and CLL is over 50% of the market in the U.S. and similarly growing robustly. In terms of patient volume, the BTK class represents about 50% of U.S. CLL patients. And as we've mentioned, Brukinza is the BTK leader in new patient starts in CLL. Given its differentiated profile, we believe Brukinza can further expand its lead in the BTK class. As you think about Brukinza as a continuous treatment, it's important to consider the stacking effect of patients that remain on therapy. In 2024, about one-third of Brukinza's U.S. Revenue came from new patients, and two-thirds came from patients that were already on therapy as we started 2024, which means we have several years of revenue growth from our increasing new patient share levels. As you can see in the chart, the remainder of patient volume beyond BTK is split between fixed-duration regimens, BCL-2 venetoclax, and chemo. Currently approved ven-based fixed-duration regimens are not for all patients, and over half of newly diagnosed patients have one or more high-risk features, where ven-based regimen treatment is associated with shorter PFS. Amplify, despite enrolling a fit, non-representative patient population that excluded patients with these risk factors, nonetheless confirmed these shorter PFS endpoints, demonstrated low MRD rates that do not correlate with durable remission, and brought along safety challenges. Given the challenges with current fixed-duration regimens and Brukinza's best-in-class profile, we see additional opportunity for Brukinza monotherapy to continue to take share from these treatment options. And beyond expansion of BTK monotherapy, we believe we have the opportunity for a franchise leadership strategy with Sonro and our BTK degrader that has the potential to far surpass the other existing treatment options and fulfill the needs of all patients with CLL, regardless of risk profile. On that note, now over to you, Matt. Thanks, Matt. I would like to take a few minutes to highlight the rest of our portfolio. Prior to 2022, BeiGene's growth was primarily driven by zanubrutinib and tislelizumab. Over the past three years, the portfolio has undergone significant transformation. For hematology, we now have three cornerstone assets, each with multi-billion-dollar market potential. The solid tumor portfolio has transitioned from a broad immuno-oncology and the pan-tumor strategy to a disease-focused approach. The pipeline targets lung, breast, and gastrointestinal cancers, focusing on critical signaling pathways and the TAA-driven therapies supported by various technology platforms. Our R&D productivity has been remarkable and sets us apart from others in the industry. In 2024 alone, we put 13 new molecular entities into the clinic, which is more than any of our peers, above even the largest pharma companies in the industry, and these assets are some of the most exciting ones in all of oncology. In addition to strengthening our drug discovery capability, we have assembled an internal global clinical development team with CIAs in 37 countries, optimizing clinical process for superior execution. Our fast-to-POC strategy consistently surpasses industry benchmarks. For instance, our CDK4 inhibitor trials achieved an average of just 6.4 weeks per dose level, and they enrolled over 180 patients within 14 months, a remarkable feat mirrored across all early programs. In addition, we're enhancing late-stage trial efficiency as well. Recently, we completed phase 3 enrollment of the CELESTIAL TN-CLL study, recruiting nearly 700 patients across 20 countries and 200-plus sites in just 14 months. It is worth noting that over 75% of the patients in these two studies were enrolled from the United States, Europe, Latin America, Australia, and Japan. Our speed and cost advantage have allowed us to advance one of the most promising pipelines in the industry. This slide highlights some of our scientifically exciting programs, many of which we believe have the best-in-class or first-in-class potential in significant markets. I will take you through each of these assets in a little bit more detail in the following slides. Despite the success of CDK4/6 inhibitors, their dose-limiting toxicities highlight unmet medical needs. A CDK4-specific inhibitor can avoid CDK6-related toxicities. BGB-43395 has the potential to be the best-in-class CDK4 inhibitor due to its superior selectivity and potency compared to Pfizer's palbociclib. We're observing lower hematological toxicities aligning with its better selectivity, and it might be dosed higher to achieve better target inhibition. As shown in the graph, BGB-43395 achieved 80% TK1 inhibition at dose level A, similar to a palbociclib at the RP2D, and at dose level B, 43395 further improved the TK1 inhibition to 95%. The proof-of-concept data is expected in the first half of this year. KRAS mutations are found in almost one out of five cancer patients. Unlike pan-RAS inhibitors such as RMC-6236 from Revolution Medicines, pan-KRAS inhibitors spare HRAS and NRAS, possibly offering a better therapeutic window by not inhibiting the RAS pathway in normal tissues. This molecule began clinical trials in November 2024. B7-H4 is expressed in several solid tumors, including breast, ovarian, and endometrial cancers. Over 70 patients have enrolled across seven dose levels, showing responses in various tumor types and at multiple dose levels. We believe we have a first-in-class opportunity here. EGFR CDAC, a first-in-class degrader with broader EGFR mutation coverage and a sparing wild-type EGFR, showed a strong efficacy in both osimertinib-sensitive and resistant preclinical models. It entered the clinical trial in December 2024. The development pathway is quite straightforward, intended as an add-on to the third-generation EGFR TKI for frontline, adjuvant, and locally advanced non-small cell lung cancer. MTAP deletions occur in one of seven cancer patients. Both PRMT5 and MAT2A inhibitors cause cell death in MTAP-deleted tumors and show strong synergy in pre-clinical models. BeOne Medicines is the only company with clinical stage assets for both. Our PRMT5 inhibitor stands out for its potency, selectivity, and brain penetration. Our MAT2A inhibitor also penetrates the brain and demonstrates superior potency in pre-clinical models. We will begin the combination study of these two molecules in the second half of 2025. IRAK4 is essential for TLR and the interleukin-1 receptor pathway. Sanofi/Kymera's KT-474 showed a near-complete IRAK4 degradation in blood, but only 50%-70% in skin. We developed BGB-45035 to fully degrade IRAK4 in target tissues and avoid KT-474's cardiovascular risks. At 5 mg QD, BGB-45035 achieved complete IRAK4 degradation in blood. phase 2 starts in late 2025, with tissue degradation data expected this year. And finally, I wanted to highlight a few of our key pipeline value inflection points. Our late-stage hematology assets have several significant milestones in 2025, including phase 2 trial readouts that may support accelerated approval submissions, as well as the initiation of phase 3 pivotal trials for both Sonro and our BTK degrader, including the planned head-to-head trial versus Pirto. Turning to our early-stage pipeline, as you have heard, we have a number of proof concept catalysts expected for our early-stage pipeline across multiple modalities and therapeutic areas. We look forward to sharing more data in future updates. With that, I'd like to pass it over to Aaron to review the financials. Thanks, Lai. 2024 was a pivotal year of growth and an affirmation of our path to sustainability. We generated strong top-line revenue growth with total sales of $3.8 billion for the year as compared to $2.5 billion in 2023. As revenue grew by 55% as compared to last year, with product revenues increasing by 73%, growth was seen across all key products and markets, which puts us in a position of strength as we enter 2025. Focusing on our fourth quarter results, total revenue for the quarter was $1.1 billion, with Q4 2024 product revenue growth of 77% compared to Q4 of last year. Consistent with recent trends, we see a broadening of our revenue base. The United States represented 55% of total revenues in the quarter, with Europe contributing another 10%. Sales of Brukinza totaled $828 million in Q4, representing 100% growth as compared to Q4 2023. In the United States, Brukinza growth was driven by demand, given our expanding leadership in new patient share in CLL, as well as other approved B-cell malignancies, where Brukinza continues to have the broadest label in the BTK inhibitor class. Please note that this class does experience seasonality in the U.S., with Q4 and Q2 being quarters of seasonally high sales. In addition, the United States' 2024 Q4 sales were also positively impacted by the timing of customer orders of approximately $30 million. In Europe, Brukinza continued its growth trajectory in Q4, culminating a full year where the business nearly tripled. We continue to grow share in Europe, where we are earlier in the product launch cycle as compared to the United States. Brukinza remains the leading BTKI in China, and as we've highlighted before, we are in the early stages of launch in key rest-of-world markets with large opportunities such as Brazil and Japan. We look forward to continuing to execute our plans to bring Brukinza to patients in these markets. Tevimbra revenue of $154 million resulted in 20% growth as compared to Q4 of 2023. We remain the market leader in China with the broadest NRDL label coverage in the class. Commercialization efforts for Tevimbra are ongoing in other markets, including the U.S. and Europe, following recent regulatory approvals. We are launching in these markets in a targeted fashion and look forward to sharing updates over the course of 2025. Amgen in-licensed products were also strong key contributors to performance, with $101 million of revenue in Q4, representing growth of 98% as compared to Q4 of 2023. Walking through our operating P&L, and my comments will be on a GAAP basis. Product gross margin was 85.6% for Q4, an increase of 2.4 percentage points versus last year, largely due to favorable mix and cost of sales productivity for Brukinza and Tevimbra. Operating expenses totaled $1 billion and included $60 million in research and development expense associated with the in-license of our MAT2A inhibitor announced in December. The growth in OpEx supported capability build to deliver near and long-term revenue growth and to rapidly advance our robust and differentiated innovative pipeline. Our strong revenue growth and value-focused investment philosophy has resulted in significant operating leverage, with product revenue growing more than five times faster than expenses in the fourth quarter. This resulted in meaningful improvement in GAAP and non-GAAP operating results for Q4 2024 compared to Q4 of the prior year, and the achievement of full-year non-GAAP breakeven. Q4 delivered $79 million in adjusted income from operations, achieving our third consecutive quarter of non-GAAP operating income. As mentioned, these results included the $60 million expense from the in-license of our MAT2A inhibitor. Our focus on operating leverage has translated into a second consecutive quarter of positive operating cash flow generation, resulting in improved cash utilization on a full-year basis. These are key metrics for the company as we transition to a self-sustaining enterprise. Now turning to capital allocation, where we follow a disciplined investment philosophy to support our dual mandate of both growth and sustainability. At the center are conservative financial policies that serve as a balance to the inherent risk-taking associated with being a leading, high-growth, innovative biopharmaceutical company. Having a strong balance sheet in our industry is a competitive advantage, and we are committed to continuing to prioritize its strength. We are in an excellent position as we close 2024 with $2.6 billion in cash while advancing towards sustained cash flow generation. We will continue to invest in our differentiated commercial assets and geographies to deliver profitable growth and bring our innovative medicines to more patients. At the same time, we will fuel our innovation engine with its unique and differentiated advantages in both time and cost, particularly through proof of concept. Value-creating business development plays an important role in our strategy by providing access to the best external science, particularly for assets that complement our internal portfolio. Consistent with previous collaborations, we will actively explore partnerships that strengthen our business. Now turning to our 2025 guidance, which assumes late January exchange rates and no potential new business development activity. We expect another strong year of revenue growth given our leadership for Brukinza. We anticipate that the U.S. Will continue to gain new patient share and also benefit from year-over-year lapping of 2024 new patient starts. We assume relatively stable net pricing for BRUKINZA in the U.S. in 2025. This is supported by our special small manufacturer designation, which layers in the increases in manufacturer liabilities for Medicare Part D benefit redesign over a five-year period. Growth is also anticipated from continued global expansion in both Europe and other important rest-of-world markets. We project revenue to be between $4.9 billion and $5.3 billion. At these levels, foreign exchange represents an approximate 1% headwind for the year. As you consider quarterly phasing in your models, please note the seasonal patterns and customer order timing that I previously mentioned. Our GAAP gross margin percentage is assumed to be in the mid-80% range, and it is anticipated to continue to benefit from improved mix and production efficiencies as compared to full year 2024. This guidance contemplates the potential impact in our understanding of current form from new U.S. tariffs on imports. Incremental costs from these tariffs are anticipated to be modest for us, given our margin structure and the degree of manufacturing for BRUKINZA that is conducted in the United States. This does not contemplate unannounced additional measures, which may change this outlook. Operating expenses on a GAAP basis are forecast to be between $4.1 billion and $4.4 billion. Our investments support key growth in both commercial and research at a pace that continues to deliver meaningful operating leverage. This is demonstrated by significant reductions in expenses as a percentage of sales. Non-GAAP operating expenses are expected to track with our GAAP guidance, with reconciling items remaining unchanged from existing practice. And finally, we are affirming our prior commitments to achieve full-year GAAP operating breakeven in 2025 and generate positive cash flow from operations for the year. And with that, I will turn the call back to Dan. Thanks, Aaron. We are now ready for Q&A. I kindly ask participants to limit themselves to one question to ensure we have time to hear from as many attendees as possible. Operator, we are ready for the first question. If you would like to ask a question, please use the raise hand icon, which can be found at the bottom of the webinar application. When you are called upon, please unmute your line and ask your question. We will now take a minute for the queue to assemble. Our first question comes from Kelly Shi at Jefferies. Please unmute your line and ask your question. Congrats on the impressive progress to the BeOne team, and thanks for taking our questions. For 2025, the guided full-year revenue guidance is $4.9 billion-$5.3 billion. Could you please walk us through the key assumptions for the initial guidance, and what could be the key factors that determine where the final number lands in the range of this guidance? And very quickly, I just want to confirm, now we have B7-H4 ADC and the CDK2 inhibitor moved up to first half of this year for data disclosure, just to confirm on that. Thank you very much. Thanks, Kelly. This is Aaron. I'll answer the first part of your question and then hand it over to Lai. With respect to our 2025 revenue guidance, we expect another strong year of revenue growth given our leadership for BRUKINZA. We're anticipating that in the U.S., we'll continue to gain share. And as I said in my prepared remarks, we also will benefit from the year-over-year lapping of 2024 new patient starts. This growth is against the backdrop, as I said, of a fairly stable net pricing environment in the U.S. And we do expect strong growth to continue from our global expansion. I mentioned in Europe, in 2024, we nearly tripled. And we have other important rest-of-world markets where we're really early. We're first launching in Japan in Q1 of this year, as an example, and that's a meaningful market for BRUKINZA. We're not providing quarterly guidance, although I did provide some commentary on the seasonality of the BTKI class, and with second quarter and fourth quarter being typically strongest. But overall, we feel really confident about how we're entering the year following a really strong 2024. And with that, maybe I'll hand it over to Lai. Yeah, thanks, Kelly, for the question. We plan to provide the first data disclosure for both the B7-H4 ADC as well as the CDK4 at ASCO. So this is for the first half of this year. Thank you very much. Our next question comes from Sean Laaman at Morgan Stanley & Co. Please unmute your line and ask your question. Good morning, everyone. Sorry about that. Good afternoon, everyone. Thanks for your presentation. I hope everyone's well. My question also relates to guidance. So you're surpassing Calquence now in terms of share. You're growing a lot faster than them, but they are still going, still growing. The cadence of their growth seems to be plateauing a little bit over the last few quarters. I'm sort of wondering in the context of guidance what the feedback is that you get from clinicians on the viability of that drug longer term, and maybe a bit longer dated, but any thoughts around what impact there might be from potential any approval of the doublet with B? Yeah, sure. Happy to address that question. And yeah, we definitely see that when we look at our overall growth, we've been very robust comparing fourth quarter of 2024 to fourth quarter of 2023. And also our full-year growth is very robust comparing 2024 to 2023. To your question around the Calquence, we see that their growth rates are substantially less strong in that particular timeframe. John, why don't you go ahead and make an additional comment? Yeah, in terms of the doublet, I think, look, we've shared a lot of data earlier in this call. The things you need for a fixed duration treatment are things that don't look very impressive in that study. It is a successful study in terms of beating in an ultra-fit population that represents maybe the healthier quarter of patients in the real-world scenario. It's able to beat chemo on PFS at 36 months. That's what that study shows. The MRD negativity is statistically worse, as we showed earlier in the slides, and much lower than any precedent data that's ever existed before, despite being in this ultra-fit, highly selected population. The safety data is not what you'd hope to see. And then you look at the PFS data straight out. Again, it doesn't compare favorably to precedent data. It doesn't compare favorably to I/V, and it certainly doesn't compare favorably to a continuous BRUKINZA therapy. So I think from that perspective, look, it's a study which has met a primary endpoint that is not that relevant. And I'm sure that they will market as much as they can about it and try to do their best to drive their commercial sales. They're a very powerful and successful marketing organization. But I think ultimately the data speaks for itself very clearly. And when people use that combination, their experience is highly likely to be in line with that data. So I think this is more of the same. As we looked at monotherapy, the story has been great around the Calquence. But as we look at monotherapy and as people actually are using the medicines and as the data matures and they use it more and more, it's very clear to us on the efficacy story. We have a strong belief that we've laid out here that Zanu is a spectacular medicine that's proven in a head-to-head trial, but it's more efficacious than I, so Z is greater than I. And I has run a study against A, but in that study, they failed to show superiority. They have a hazard ratio of one. And again, their milestone PFS is 8% worse than the data that's previously shown. So with that said, we don't view this as a major threat. And John, if I can just add a little bit of the color commentary around what we hear from physicians related to that part of the question. In there, I think we continue to hear about safety and handling concerns related to venetoclax and the complexity and the burdensome nature of patient management on AV, as well as on AVO, if you think about the triplet. And then when you look at the data that added acalabrutinib to VO, again, there, the outcomes don't suggest an overall favorable profile when you start to look at safety. So I think one of the things that we'll have to do and we'll continue to hear from physicians is look at what labeling ends up looking like for that doublet. And that'll be in the context of all those other factors. Right. Thank you. Comprehensive. I'll jump back in the queue. Appreciate it. Our next question comes from Andrew Berens at Leerink Partners. Please unmute your line and ask your question. Hi, thanks. Nice job on your first live earnings release. There's a big readout in gastric cancer, Zani, and Tizzle, and just wondering what you're looking for in RMC, what it could mean to the franchises, and also what's the company's commitment to breast cancer efforts that Jazz has embarked upon. And then based on John's squeeze-to-juice comments, I know you're not promoting fixed duration Brukinza yet, but are you seeing or expecting to see Brukinza to be used off-label in fixed duration regimens? Is there a chance to get a compendium endorsement ahead of the pivotal data? Thanks. Yeah, thank you so much for the question. I will answer the first part of the question related to Zani, and then I'll pass to my colleague, Matt, to answer the second part of the question. In terms of Zani, this is actually a three-arm design, as you pointed out. The third arm, which you mentioned, is the combination of the Tisle plus Zani plus the chemo. We believe this will further broaden the label for our Tisle in the first-line gastric cancer. Right now, Tisle has a label in the HER2 negative patient population. And if this trial is successful, we'll further broaden the label. As you're aware of, this trial now, the readouts will be in the second half of 2025. I'd like to point that out. This is an events-driven trial. So purely, this is based on the events' occurrence. With that, I'll probably. Oh, you have that question related to the breast cancer side. But we're still in discussion with our partner around the development of the Zani in the breast cancer franchise. Sure. And then maybe I could talk about spontaneous use on Brukinza. I certainly understand the nature of the question, given our best-in-class profile for BTKs. But I think it's also important to remember that we don't currently have a BTK plus ven approved in the U.S. And also, when we look at things like NCCN guidelines and compendia, we don't yet have a Brukinza listing in that setting. Now, on the other hand, we did recently have data from the ALPINE study. And while that was MRD-guided rather than purely fixed duration, there are certainly thoughts about what that could mean in the future. Thank you. Our next question comes from Jessica Fye at J.P. Morgan. Please unmute your line and ask your question. Great. Good morning. And congrats on the strong guidance. Question about how you're thinking about the upcoming Proto readouts, both in frontline CLL and the data they're generating against Imbruvica. What are you going to be watching for there, and what will be the appropriate BRUKINZA cross-trial comparisons? I.e., should investors line those hazard ratios up with your trials, or why or why not? I appreciate you guys are taking your degrader head-to-head against pirtobrutinib, but thinking about potential nearer-term competitive dynamics. Thank you. Y eah, thank you so much for the question. Pirtobrutinib does have two phase 3 trials ongoing in the frontline CLL, although the second trial is a mixed population. The first trial, I think you're referring to, is the 3-1-3 study, which is pirtobrutinib is being compared to chemoimmunotherapy. I do want to highlight chemoimmunotherapy is no longer really a standard care for the frontline treatment naive CLL. This study, the readout does not necessarily mean we'll change the practice. This will be a study similar to what the AMPLIFY did, which is against another standard of care. The second study is an interesting design. This is a mixed population with up to 30% patients being the treatment-naive frontline CLL patients, and while the others will be the relapsed refractory CLL patients. This study, I actually want to point out, is with ORR as a primary endpoint with non-inferiority study design. Even if this study has the positive readout, we don't believe this will be practice-changing, and also, the comparator here is ibrutinib, not the best-in-class BTK inhibitor, zanubrutinib. I think we're eagerly watching this data readouts. I think for Proto to take any significant share in the frontline, that will require us really compare to truly a standard care and with a much longer follow-up. So we do not believe this in the short term will change the dynamics in the adaptation of the BTK inhibitor in the frontline. Proto is probably more positioned as the BTK inhibitor after the patient's finishing treatment with the covalent BTK inhibitor. We're very excited about our BTK degrader. From our data report at ASH, we believe this molecule demonstrated better safety and better efficacy compared to Proto. This is why we're going ahead with a head-to-head trial versus Proto. Excited to get this trial going and to potentially provide patients with a better treatment option after you're finishing covalent BTK inhibitor. Great. Thank you. Our next question comes from Yigal Nochomovitz from Citigroup. Please unmute your line and ask your question. Thank you. For the strong quarter. Hopefully, you can hear me. I had a question regarding the comment on the patent settlement for Brukinza. First of all, was that in keeping with your expectations for 2037? But then more importantly, assuming you get combo data with Sonro approved, is there any way that could protect you from a generic if you were to work on a fixed-dose oral combo? And are you working on that strategy? Thank you. Thanks for the question, Yigal. So certainly, we've publicly disclosed where we are with respect to our Brukinza patent protection. And as you said, mid-2037 is what we've talked about as a starting point. As it relates to our broader franchise, certainly, when you think about the combination of our assets, we're really seeking to fulfill all dimensions of the patient journey. And that is a long-lived franchise. Our assets beyond Brukinza, obviously being still in development, have patent protection well beyond that point in time. So we see this as a franchise that's durable, sustainable, most importantly, will fulfill significant unmet need in the market and position best-in-class treatments for all patients with CLL. Thanks for the question. Okay. Okay. Thank you. Our next question comes from Reni Benjamin at Citizens JMP. Please unmute your line and ask your question. Hey, congratulations on a great 2024. Great. Can you guys hear me? Yes. Oh, got it. Thank you. Well, congratulations on an amazing 2024 and even more amazing 2025 guidance. My question's on the completion of enrollment of the CELESTIAL study. Can you talk a little bit about how you're thinking about the event rates going forward, when we might expect top-line data and a potential NDA submission? Thank you. Yeah, thank you very much for the question. Yeah, we're very excited about this study being able to finish enrollment in just about 14 months. This, again, demonstrates our ability to really execute late-stage clinical trials. In terms of the events side of it, we did not guide it. This study is an events-driven PFS with the primary endpoint. We're eagerly, as you are, waiting for the study to read out. But, as the control arm is the VO, so it will take a little time to read out. Thank you. Our next question comes from Michael Qian at Goldman Sachs & Co. Please unmute your line and ask your question. Thank you, Mr. Oyler, for taking my questions. Very great quarter and fourth quarter of 2024. My question is really regarding the Sonrotoclax because in the first line, CLL, how do you see the potential patients' preference? Are they going to prefer fixed-dose duration treatment, or it's going to be still more on BTK immunotherapies? The reason I'm asking this is because the slides that Matt was showing, after about a decade of prescription of BTKI in the first line, we still see only about 50% of patients actually on BTKI, while the rest of the 50% is on other treatment. So I'm kind of wondering, when the fixed duration comes into the market, what's going to be their patients' and physicians' preference? And also, what could potentially be the potential impact on the whole franchise sales, given that fixed duration is definitely going to be triggering a shorter duration of treatment versus Brukinza itself? So I'm wondering how you think about the overall franchise impact when the fixed duration is going to come into the market. Or you're thinking about potentially we're going to start with fixed duration, then the patient is going to switch back to Brukinza immunotherapy for longer-term maintenance therapy. Thank you. Thanks for the great question. I think, first of all, fixed duration means lots of things. Chemo's fixed duration. I think you have venetoclax VO combinations, and then I think you have VI, which is not approved in the U.S. You have AV, which has a study that will seek approval, and we'll see how that plays out. I think that what we've laid out for you is when you actually look at this data versus continuous Brukinza, continuous Brukinza looks like a better option for most patients. I think also fixed duration should not be confused with intermittent therapy. Really, what you're talking about in this study, highly selected, ultra-fit population, only relevant for a quarter of the patients, not deletion 17p patients, which have a worse outcome, not older patients, not less healthy patients. In that population, you're still seeing close to a quarter of the patients progress within three years. Remember, they were on treatment for 14 months, right? That's only 20 months of being off treatment. And they've progressed a quarter of the patients. And if you look at the shape of that curve, you can jump back to it. Look at it right after 36 months. Just look at it. And again, highly selected. This is as good as it could ever possibly get. The real-world experience is going to be in much less healthy patients with much worse outcome. And if you just compare that to a continuous therapy, it's underwhelming. It's just underwhelming. So I think if that's the hurdle you're looking at, you really have a choice between VO, which is a huge tax burden, a huge burden on patients. Even this VI, when you actually look at the patient journey on it, it's no better. It's probably worse than chemo and the burden to a patient of the hospitalization and the monitoring associated with venetoclax. We don't anticipate that to dramatically change this percentage of fixed duration versus continuous therapy. Actually, we think there's an opportunity for continuous therapy to try to work its way more broadly into some of those patients, the 50% that aren't on continuous therapy today. Of course, we're the leader in that space. More importantly, as we've laid out, Sonro plus Brukinza finally looks like it's a fixed duration where the squeeze and the juice make sense together. That would be a first. I think we do believe that if we can continue to mature that data, and it looks the way it is, that for the patients that are on fixed duration, which is roughly half the patients, whether it's chemo, whether it's other venetoclax-based therapies, this will stand out as a much better option than all of that. From that perspective, we should really be able to expand into that area. All that said, still, Brukinza monotherapy, we believe, has a strong role in this. For patients that are hard to treat, you have to have a lot of confidence to take people off and stop therapy. Everyone likes it. The promise is good. If you don't have MRD negativity, that's a bold thing to do. If you don't have PFS that really does look better, it's a hard thing to do. I think that with more and more experience, we are very comfortable with the role of continuous monotherapy moving on. We believe with the Sonro combinations, there's huge opportunity in half of the patients we're really not reaching right now. I think from the other perspective, just simply put, this is a franchise that will require combinations that will have for different types of patients continuous therapy and fixed duration. The three agents we have, I think, as we've said, single-agent combinations, we can cover this entire space, and we probably can cover it with better outcomes for patients in every setting. We're excited about that. Even fixed duration, even with Sonro plus Brukinza, it's not going to be a fixed duration where you stop and there's never any progression. There will be progression, and there will be retreatments and relapse refractory market, which will be substantial. It's not yet a cure. That's far from that. T hank you. Got it. That's very clear. Thank you, John. Our next question comes from Michael Schmidt at Guggenheim Partners. Please unmute your line and ask your question. Hey, guys. This is Michael here. Congrats on the progress in 2024, and we're definitely looking forward to the year ahead. Just to follow up on CDK4, you mentioned that the data will be at ASCO. If I heard that correctly, I guess, how are you setting expectations for that data disclosure? And what additional efficacy signals would you want to see to further support your planned phase 3 development and also be differentiated from other programs? Thank you. So can I ask you to repeat your question on which data you're referring to? CDK4. CDK4. Okay. Got it. Yeah. Thank you so much for the question. The CDK4, we're already seeing very interesting data from our early dose escalation. We're really in the safety expansion cohort trying to determine what will be our dose taking forward. The set of data, as I mentioned today, we are very excited about, which is consistent with our preclinical hypothesis with better selectivity and the better potency. Seems like now this is translating to clearly in the clinical side of it, where it's less chemotoxicity, but we're also seeing a better target inhibition with the TK1 assay. So with that, and we are going to analyze our data as the data come in and really make a decision whether or not to start in the pivotal trial in the later part of this year or early next year. Got it. Thanks a lot, guys. Our next question comes from Jayna Ahn at TD Cowen. Please unmute your line and ask your question. Thank you. Hi. Yeah, thanks. This is Jayna Ahn for Yaron. Thanks for taking my question. Congrats on a great quarter and 2025 guidance. Just a few quick ones from me. Number one, what are you expecting on Tevimbra in the U.S. and EU for your 2025 guidance? And number two, on your degrader, I know you're evaluating some chemo-free combinations, such as with BRUKINZA, Sonro, or a CD20 bispecific. Of these, what are you most excited about, and how confident are you that you can maybe move your degrader up into earlier lines in CLL? Thanks so much. So I'll start with the question. Thank you so much. Tevimbra continues its strong growth trajectory. You can certainly reflect on our 2024 performance. Broadly, obviously, we continue to be the leading PD-1 in China. And we have several new indications that are NRDL eligible this year. And we look forward to continuing to commercialize those and expand our leadership with the broadest NRDL reimbursement coverage in the class. And I would reflect 2024 had a pricing impact that was not immaterial. And still, it showed extreme, really strong growth. 2025 doesn't have that dynamic. As we think about the launches in both the U.S. and Europe, we're in very early days. As I mentioned in my prepared remarks, we are investing in a targeted way. We like the response we're seeing in the market, but at this point, we'll continue to keep you all updated in 2025 as we get more experience with the product in the marketplace. So with that, I'll hand it over to Li. Yeah. And as for the question related to degrader, the platform trial, we're actually excited about all three, as you mentioned, in terms of in combination with Sonro, as well as combination with Brukinza and the CD20, CD3 bispecific. The reason for that is they're probably used for different indications. We do not believe that degrader is only positioned for CLL. There's definitely utility outside of CLL. For CLL side of it, probably we'll be more excited to see the data in terms of combination with Sonro as well as with Brukinza. But outside CLL, there's other indolent lymphomas, which BTK has definitely demonstrated efficacy with single combination with CD20, CD3 bispecific, especially particularly probably for follicular lymphoma. Marginal zone will be quite exciting. So we are eagerly waiting for the data readout from that platform trial. Thanks so much. There are no further questions. I will turn the call over to John Oyler for closing remarks. Thank you. I just wanted to thank you all for joining us today and for the thoughtful questions. I think that, as you know, our vision at the company is to do great science, make truly impactful medicines that can help patients with cancer, and to pursue a business model which is different. For example, with our internal 3,700-person global clinical team, so that we can make medicines faster and more cost-effectively than other companies, which enables you to have an attractive and preferential set of returns with our company. I think today, the goal is also to show that we can do that and bring medicines more affordably and more accessibly to patients here in the U.S. and around the world, and we are well on our way to doing that. And I think we're doing that in a framework that is economic, that we're showing it works. And whether it's the speed of the trial enrollments, whether it's the quality of the data that you see in this presentation, I think we're well on the way to living up to that very bold mission and vision that we have. And I just want to conclude the call with thanking all of our investors and analysts for their help in supporting the company, for the team here, for all they're doing, and the clinicians and the patients across the world that have really helped drive the data collection to help us understand which of the medicines we're developing are really impactful so that we can put our resources behind them and bring them to patients. And we very much look forward to continuing this journey with all of you. Thank you for permitting us to live this real privileged dream that we're in the middle of, which is a lot of fun, so thank you.