Okay. Thank you, everyone. Appreciate that. With that, happy to have with me Dr. Mehrdad Mobasher, CMO of Hematology from BeiGene, and Mark Lanasa, CMO of Solid Tumors from BeiGene. Thank you both for joining us. Appreciate it. Before we get into any pipeline-related and BRUKINSA-related Q&A, I thought it might be good just to level set for the audience, if you could both just provide a quick overview of what you think some of the key inflection points have been across your respective areas of work at BeiGene for this year. Sure, maybe I'll start first with hematology. So with hematology, this year, we have really shown that we are really one of the global emerging leaders in hematology drug development. We started the year fresh out of releasing the data from Alpine study, which was our head-to-head study of BRUKINSA versus ibrutinib in CLL. And we released the data as a late breaker abstract at ASH, end of last year, simultaneously published in New England Journal of Medicine. And that led to an approval early this year. So we had our CLL approval earlier this year, which was our fourth approval with BRUKINSA. And with the totality of data this year, we have really cemented BRUKINSA as the BTK inhibitor of choice. We're not done with BRUKINSA. We continue to work with this asset. This year, we submitted, and now we recently announced that we have an sNDA pending for follicular lymphoma, which can potentially be our fifth indication. So we have the largest number of indications for any BTK inhibitor. Other than the studies that are ongoing with BRUKINSA, we are moving the rest of our pipeline fast, very forward. And the way that we are putting our pipeline assets that are purposefully designed for this will continue to cement our leadership again in CLL and also other B-cell malignancies, whether it's with fixed durations or the way that we are thinking about sequencing, to remain leaders in these malignancies. And also, we are increasing our footprint outside B-cell malignancies that we have historically been focusing on. With the number of patients that we have enrolled this year and the data that we have released, we are entering AML, MDS, multiple myeloma with our BCL-2 inhibitor and with our BTK degrader. We have potential to go to more aggressive lymphomas like Richter's transformation or large B-cell lymphoma. Great. And actually, I might have forgotten to read a disclosure statement at the start, so let me just do that now. For important disclosures, please see the Morgan Stanley Research Disclosure website at www.morganstanley.com/researchdisclosures. And if you have any questions, please reach out to your Morgan Stanley sales representative. Mark, go ahead, please. Sorry about that. Great. Oh, no problem. And thank you for the opportunity to be here this morning. We're very glad to be able to present at this important conference. So it's been an exciting year for solid tumors as well. First, I would say that we continue to have great success with our foundational molecule, which is our PD-1 inhibitor, tislelizumab. We have announced the successful phase III studies and ITT analysis of frontline gastric chemo combo and HER2 negative. Recently presented frontline data for extensive stage small cell lung cancer at World Lung Congress, sort of positive and frontline there. And we have also announced positive frontline data in our 315 study with tislelizumab, which is early stage neoadjuvant, adjuvant on small cell lung cancer. So, very happy about the great progress and success we're seeing there, and we're working hard to turn those successful studies into global regulatory successes and patient access. Second, we're making really great progress with our next wave immuno-oncology portfolio. We have a number of TIGIT abstracts that we look forward to sharing at the upcoming ESMO, but also making good progress with other targets, including LAG-3, TIM-3, and others. We have exciting new targets in the immuno-oncology space, including CCR8, HPK-1, and DGK-zeta. And then last, we recently had an R&D day, where we disclosed a number of new targets that we'll be bringing into the clinic over the next 12-15 months, and we think we have a number of really compelling medicines that will enter the clinic, including a selective inhibitor of CDK4, our first solid tumor bivalent degrader targeting EGFR, and KRAS inhibitor, and our first internal ADCs targeting B7-H3, as well as other targets. Great. Great, so let's do this. Maybe we can talk about hematology first, and we can go to solid tumors. Within hematology, I think the key areas we should touch on are BRUKINSA, obviously, some product launches, and then maybe the BTK degrader as well. Sure. So for BRUKINSA first, you alluded to how the launch has been going- Mm-hmm. Especially with the indication expansion to CLL, FL. I'd be curious to hear any feedback you've received from the field on, from both doctors who are prescribing actively the therapy and, you know, what's motivated them to choose BRUKINSA versus other BTK inhibitors. And then also on the flip side, physicians that aren't quite at that level yet, you know, what's been holding certain physicians back from switching from maybe Calquence and ibrutinib to BRUKINSA, if you've received that sort of feedback? Got it. Got it. So we are closely working with the physician community. From my side, no, more probably with the KOL community, but I'm closely in touch with my colleagues in medical affairs and commercial, who talk to everybody who treats cancer patients. And the feedback has been positive, which was what we were expecting, particularly after we released the Alpine data. And again, when they put the totality of the data, not just in CLL, but with all those other indications. That across the board, the efficacy has been pretty impressive to them, and also particularly safety. That BRUKINSA was a lot safer than what they were used to, what particularly when they were using ibrutinib. We had two head-to-head studies, and the Alpine was the second one that read out, so give them real confidence in the safety that they can see in their patients. So with the CLL approval, obviously we see that they are using that more, for CLL. And it has led to more usage even in the other diseases. Because once physicians start using one drug, they're more comfortable, with using it in other diseases as well, the other indications that we have. So those who are using it are very comfortable, with what they are seeing in terms of safety. They're very impressed with the efficacy. We often talk about PFS being the gold standard for CLL, but the depth of response that they even see with BRUKINSA is something that they are closely communicating to me. From the flip side, people who haven't been using BRUKINSA yet, we know that physicians, it's hard to make them change their habits. And ibrutinib was a drug that they have been using for many years, so they need a little bit more time, and a little more hands-on experience. Now with CLL, that's already using it in CLL, well, it will take time for them to make it their BTK of choice, for all of their diseases and CLL. But again, we are confident that that will happen. Got it. Got it. And you've mentioned previously that updated Alpine data- Mm-hmm. C ould be presented at ASH 2023. What should we expect to learn there, and what are you hoping that this data set can further help de-risk about the profile for the, for the molecule? Sure. Let's talk about the Alpine data that we showed last year. Sure. So Alpine was a well-designed, well-conducted study, and that analysis was a planned analysis based on number of events. So it was triggered at the time that it was triggered, which was 29.6 months of follow-up. Which in relapsed refractory CLL is a very meaningful follow-up time, and we showed significant progression-free survival, and actually really important safety difference between BRUKINSA and ibrutinib. One of the things, again, physicians always want more follow-up and all that, and other studies, similar study that acalabrutinib did. They had a non-inferiority study in a subset of patients, and they released their data at 40-month follow-up. So we thought it's the best option for us is to continue the study and continue to have longer follow-up. So that's what you are gonna see at, at ASH. And I'm, I'm confident, given the shape of the curve from the beginning, when we looked at the Alpine shape curve, that we showed at ASH, they separated very early on, and they continued very nice and smooth. So with, more follow-up, we expect the same pattern to continue. Got it. Okay. Any questions on BRUKINSA before we move on to other parts of the hematology program? Pipeline, excuse me. Okay, let's move on to sonrotoclax. So with question one, how do you think sonrotoclax is designed to be a differentiated BCL-2 inhibitor versus some of the others that are currently under evaluation across, across the industry? Mm-hmm. Yeah. So I think everybody here is aware of the BRUKINSA story, how it was designed actually by our chemists to have properties that made it a BTK inhibitor of choice or a superior BTK inhibitor. And I have to give a lot of kudos to our chemists. They took the same approach to BCL-2. So BCL-2 was a known target for actually many, many years and was not druggable. And they looked into all the unmet needs of how we can target that molecule. And they ended up with sonrotoclax, and it has several aspects. Number one, it's very potent. The drug is much more potent compared to venetoclax and all those other BCL-2 inhibitors that we now see in early development. We know that the potency of the drug that you use for diseases is actually very important. We did some preclinical models. We have shown that in wild type BCL-2, we were 14 x more potent than venetoclax. When we took the drug into the clinic, we used a PD marker as comparing venetoclax and sonrotoclax. We saw sonrotoclax is 5 x more potent than venetoclax. That gives us the chance to, when we increase the dose with safe dose, to have higher exposure of BCL-2 inhibition. So that's, I think, an important part of the drug. It's selective. It's only selective versus BCL-2 itself compared to other members of the BCL-2 family. An important characteristic that this drug has is PK characteristics. And we know sonrotoclax has a short half-life. The half-life is about four to five hours, which when we think about some of the toxicities that we see in the class, becomes important. Basically, the drug comes in the blood, and then it leaves. Venetoclax has a half-life of 26 hours and accumulates in the blood, and sonrotoclax doesn't accumulate in the blood. And that's why with venetoclax, you see all this labor-intensive lab checks, hour zero, hour eight, the next day, and also the toxicity in terms of, and the worry about TLS, tumor lysis syndrome, continues, and also neutropenia and all that. So that's why this molecule was designed such that we don't have to do all those labor-intensive work. So it becomes a little bit more usable. So every physician, academic or non-academic, in any setting, can use this drug, which is unfortunately something that venetoclax currently doesn't have. So that's why we think our drug has the best-in-class opportunities from the safety that we are predicting it for it to have, and also potency that we think it will lead to improved efficacy. And I'll say this, and I'll finish, that we have also enrolled more than 500 patients across the board, including more than 100 patients in CLL. So a lot of things that we were thinking are panning out. Okay, great. That's a good segue into the next question then. So you're starting first-line CLL/SLL program by the end of the year? Mm-hmm. Could you just kind of walk us through the design and endpoints of that study, and then highlight, you just alluded to this, highlight maybe some of the clinical data points you've seen so far that give you conviction that, this is, a high-conviction kind of program for the company? Mm-hmm. Maybe I'll start from the second question. Sure, sure. So we were monitoring our data closely, similar to how we typically do these studies. We had monotherapy with sonrotoclax in relapsed refractory CLL. Then we had combination of sonrotoclax plus BRUKINSA in relapsed refractory CLL. Then we started a cohort of frontline CLL with our combination, and we chose two doses to test in our frontline. So that's why I'm saying we have had more than 100+ patients, just 100 patients in frontline CLL. And what we saw from early on, even from monotherapy, is that we have early and deep responses. And by that I mean we have complete remissions, which is a kind of a surrogate endpoint in CLL that correlates with final outcome, and also early eradication of MRD, that is scientifically accepted to be an indicator of longer outcome and progression-free survival. Same thing with the combination. And when we compare our doublet, whether versus in-class doublets and also other doublets that are available, and venetoclax is only drug that actually has MRD negativity, we think, again, our responses are deeper, our MRD eradication is deeper and also comes in very early, which is also, we know that correlates with outcome. So after we enrolled this 100 patients, we have shown zero progression, so our progression-free survival at the current follow-up, which is relatively short, not very short, is 100%. So with all of that, we felt comfortable that we can go and do a head-to-head study in frontline CLL. The frontline CLL study that we have is actually a pretty simple design. It's one year of our doublet, BRUKINSA plus sonrotoclax, versus venetoclax and obinutuzumab, which is the most potent and pretty much the only widely accepted regimen as a comparator. The primary endpoint of this study is progression-free survival, which is a gold standard for CLL. We are collecting MRD as an important secondary endpoint. And of course, OS and responses and the stratification factors that affect the outcome of the CLL patients are being used. The study is truly global. You know, of course, U.S., Europe is a big part of the study, Asia Pacific and even Latin America. Got it. Got it. Okay, that's great. Maybe just to be mindful of time, let's pivot to the BTK degrader. Sure. My first question for you there is: How is this molecule potentially differentiated from other BTK, BTK degraders, excuse me, in development from companies like Nurix? Like, what are the, kind of the unique structural features that you think of this degrader that are worth keeping in mind? Sure. So, so one background, the degrader, this, we call it CDAC, in our company, is a platform that was built in-house. So this was the first degrader that kind of, graduated, from our research to, to clinic, now quite a while ago. So that's the, the one thing, it's homegrown. We think it's the most advanced in the field. You know, we showed at the R&D Day that, between the two studies that we have, we have enrolled, more than 50 patients. The MOA is becoming very exciting, so there's a lot of excitement about this study, and it's, it's enrolling very fast. So compared to a lot of competitors, we are, a lot ahead of them. We're a lot more advanced. Nurix has, two molecules. Their first molecule that they presented data at ASH last year has IMiD activity. Mm-hmm. But the data that they showed last year, we had some significant toxicity, including high-grade fatigue, hypertension, and higher rates of atrial fibrillation, that across the board we think is because of that IMiD activity. They have a second molecule that doesn't have IMiD activity, so it's more similar to our drug. So ours doesn't have IMiD activity. It has enrolled 50+ patients, so a lot advanced compared to their second molecule. So far, safety and efficacy, we have been very happy with what we are seeing. Got it. Got it. And each of these assets, BRUKINSA, obviously currently approved in CLL, SLL, sonrotoclax, you're starting a study there soon. Mm-hmm. You've mentioned that the BTK CDAC could also be purposed for one segment of the population there. How do you see these three agents kind of fitting into the treatment paradigm within CLL versus each other, and kind of other therapies that are out there or could be out there by the time these therapies are approved? So multi-part question, but in general, where do you see this kind of all coming together? Sure. So we actually see ourselves as a leader in CLL. I mean, after the data, the superiority data in Alpine, the only BTK inhibitor that has superiority data against another BTK inhibitor, we think that's the BTK of choice. That has given us this leadership in CLL, and we really want to strengthen that leadership in CLL. So there is a part of patients that will continue to get a BTK monotherapy in their frontline. BTK monotherapy currently is the main treatment of patients with CLL. There is a desire within the field to have time-limited therapy, fixed-duration therapy, and that comes from physicians, a lot of patients, particularly post-COVID, they want a fixed-duration treatment, and be done. So we are giving them that option with sonrotoclax, and BCL-2 inhibitors historically have been the only option with anything that you added to them, that can bring the disease level so low that you can do fixed-duration treatment. So that's what we think our frontline treatment paradigm will look in foreseeable future. And then patients who go relapse, depending if they got BTK alone, even if they got chemotherapy, those older treatment options that some people have gotten before and they're still fine, or they even got our combination or BCL-2 inhibitor in the frontline, they have other options with our assets. Whether it's our sonrotoclax in combination with an anti-CD20, repeating the same option that they got, the doublet that we gave them in the frontline, or degrader alone, or degrader with sonrotoclax. You can actually even think about the third option with the same thing. The way that we are really leading our efforts in CLL is that we think through the journey of CLL for patients from their first line all the way to their relapse, because unfortunately, we haven't cured CLL yet. They will be on a BeiGene drug. Sure. That's helpful. Final question for you on the BTK CDAC. Just remind us of timelines, kind of what can we expect to learn over the next one to two years in terms of the data? Sure. So we'll present some data at ASH. We think it's a drug that we achieve that proof of concept very early on, even with our PD markers. And that's why we have been aggressive, more sites, we have been enrolling really well within our dose escalation. It's not your typical 3 + 3 dose escalation that you have to wait for a long time. So we are backfilling, that's why our numbers are bigger. And we think next year, in 2024, we can start a potentially pivotal expansion cohorts. So the study initially was designed for two cohorts, specifically for relapsed refractory mantle cell and relapsed refractory CLL. Now we are increasing the size of those two cohorts. They will initiate in 2024, and then we'll have the data there. Got it. Okay, great. Any questions on hematology before we turn over to solid tumors? Okay, Mark, let's turn over to you. Maybe the first question on everyone's mind is, given the TIGIT program you have in your pipeline is, there was recently, recently an announcement from Roche regarding the second interim analysis from Skyscraper-01. Would just love to kind of get your take on the announcement and what you think it means, if anything, for ociperlimab? Great. Thank you again. So the recent accidental disclosure, not exactly sure how to describe it, the Skyscraper-01 interim analysis 2 data, we believe is fairly compelling additional evidence of the incremental benefit of TIGIT on top of PD-L1 and non-small cell lung cancer. So at this point, across the SKY1, CITYSCAPE, our internal data that we've shared and other external sources, we have high belief that there is that incremental benefit. Now, the question ultimately is: Is that benefit going to be statistically significant? That remains to be seen for Skyscraper-01. Will it be viewed as clinically meaningful? Now, I think in the SKY1 data, with the delta at the median of 5.5 months, that will be viewed as clinically meaningful. However, because the atezolizumab monotherapy arm underperformed, the question will be: How does atezolizumab plus tiragolumab measure up against pembrolizumab monotherapy? Therefore, we believe that in our AdvanTIG- 302 study, we made the right design decision to have pembrolizumab monotherapy as a control arm, which is the acknowledged standard of care for PD-L1- high non-small cell lung cancer, particularly here in the United States. So that study continues to enroll well. We're on track to complete accrual by the end of the year with a subsequent event-driven readout. Got it. Okay, great. You actually recently regained full rights to your TIGIT program after a mutual decision with Novartis to return the program back to BeiGene. Is there an appetite to continue to seek a partner for this program, or is it, at this point, a fully in-house program that you hope to prosecute completely independently? I can't really speak to the business development strategy, but what I'll say is that we're delighted to have regained the global rights to ociperlimab. Got it. Okay, fair enough. Just taking a step back, just recap for us what we can expect to learn from this program overall in the next six-12 months, because you obviously have multiple phase II programs currently underway, so we'd just love to hear about what you think the data flow could look like here? Yeah. So our overall development strategy with our TIGIT ociperlimab was that, again, in the context of a very strong phase II study from Roche, the CITYSCAPE study, and having supportive in-house phase I single-arm data, that we quickly moved to phase III in the PD-L1- high population. That's our 302 study. However, in other tumor types, we believe that we are able to, quickly and at favorable cost basis, deliver randomized phase II studies, so we could have high-quality data to inform subsequent phase III decisions. We initiated five studies, all relatively concurrently, so we're getting the data now relatively concurrently. We're going to be able to share data at this year's ESMO for frontline hepatocellular carcinoma and PD-L1 or PD-1 naive cervix cancer and esophageal cancer. So we're excited to share those data, and then we should also be able to talk about our next steps vis-à-vis subsequent investment decisions and two additional phase III studies and new indications. Got it. Just to kind of frame expectations there for some of these, phase II data sets coming out later this year, how would you guide people to interpret the results when they come out? What would you consider to be strong outcome versus kind of a less optimal one? So for the randomized studies, these are all, say, 100- to 120-patient studies. There's a little bit of variation. We are attempting to have our go decision based upon the combination of response rate and PFS. Now, again, we're taking in the data as it's emerging. Skyscraper-01 suggests that perhaps OS is the most compelling endpoint. Nevertheless, for these randomized data sets, we do think that we'll have confidence in whether we're able to see, again, a clinically meaningful improvement in both response rate and progression-free survival. Tislelizumab is the control, with or without a standard of care, across all three of those studies. Got it. Got it. Okay. Any questions on TIGIT? I had a couple more on other pipeline programs, but I wanted to take a pause in case there's anything people wanted to ask on, on that program specifically. Okay. So you highlighted at your recent R&D Day, multiple different mechanisms that you're exploring, kind of like TIGIT to LAG-3. So there's a lot in the early-stage IO pipeline. If I had to ask you to kind of pick one area of particular kind of internal excitement across all the different mechanisms, which would those be? So of course, we're excited about everything that we bring into the clinic and want to explore it appropriately. We are similar to the story with TIGIT. We are now initiating a series of randomized phase II studies and umbrella studies for the other co-checkpoints, such as LAG-3, TIM-3, and others. But for something to focus on, we're particularly interested in the small molecule inhibitors of kinases downstream of the T- cell receptor. So that includes HPK1 and DGK-zeta, which is a recently announced target where we recently achieved our first human dose. We're seeing interesting data emerging with HPK1. We've not disclosed that data yet. We'll look to share some of that data next year, but we are seeing immunomodulatory effects with those molecules and very excited to see what we see with DGK-zeta as an alternate pathway downstream of the T- cell receptor. Okay. That's helpful to know. Maybe my final question for you here then before we close out. Do you have a readout anticipated from the RATIONALE-315 study in the near term? Yes. Just guide us in terms of kind of what expectations are there, what you're hoping to see. So as I alluded to before, RATIONALE- 315 is a study in early-stage resectable non-small cell lung cancer, where patients receive chemo plus tislelizumab or randomized to receive either chemo with or without tislelizumab as neoadjuvant therapy, then have surgery, and then go on to, adjuvant therapy, yes or no, versus placebo. There are already benchmarking data sets that are out there. There have been other, sponsors that have reported, data in this setting. This is a study with co-primary endpoints of major pathologic response, which is measured at the time of surgery, and then event-free survival as the, ultimate time to event endpoint, which conveys clinical benefit. So what we'll be sharing is the data for major pathologic response rate, as well as the pathologic complete response rates. Again, there are benchmarking data sets that are out there, so while we discourage cross-trial comparisons, we acknowledge that the lens is the data will be assessed in that context. Got it. Okay, great. Any... I'll do a final call for questions before we close out, around 15-20 seconds or so. No? All right. Well, in that case, I hope you all found this helpful. Thanks so much to both of you for being here. Really appreciate your time. Thanks. Thanks, everyone.