Hello, 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 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. 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 the 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 Euler, our Co Founder, Chairman and CEO provide a business update Xiaobin Wu, our President and Chief Operating Officer, will provide an update on our global commercial progress Matt Shaulis, our General Manager of North America will provide an update on The U. S. Commercial performance of Burkinza Lai Huang, our Global Head of R and D will discuss our R and D and pipeline progress and Aaron Rosenberg, our CFO, will review the first quarter financial results and financial guidance.

We will then open the call to your questions. I'll pass the call over to John. John?

Thank you, Dan, and welcome everyone to our Q1 earnings call. Last quarter's call, I spoke about three priorities for 2025. The first was solidifying and deepening our hema franchise leadership. The second was advancing our prolific pipeline of internally developed assets and the third was driving superior financial performance. I'm excited to share with you how we delivered on these priorities through the first quarter. BeiGene is the only company with an discovered and wholly owned portfolio of potentially best in class [indiscernible] across all three foundational mechanisms in CLL. We believe our relentless focus on serial innovation in CLL uniquely positions us to address the full scope of unmet patient need across all lines of therapy in subpopulations. Brukinza is the best in class BTK inhibitor that serves as the backbone of our franchise. In The US, Brukinza is the leader in new patient starts for both frontline and relapsed refractory CLL and across all of its approved indications. Bruckensa possesses the broadest label of any BTKi. And for the first time, Brukinza has surpassed both ibrutinib and acalabrutinib in overall US quarterly revenue. And continues to outpace its BTKi competitors in year over year growth. This leadership follows the science and the data.

And reflects Brukenza's clear clinical differentiation. Brukinza is the only BTKi to exhibit complete and sustained inhibition. And it's the only BTKi to demonstrate superior efficacy and safety in a head to head trial against ibrutinib. And anchored by its best in class clinical data, Brukinza has now treated over two hundred thousand patients globally. Sonro our potentially best in class b c l two inhibitor, continues to advance rapidly through late stage clinical development. We've completed enrollment in our Phase III CELESTIAL trial of Sonro plus in treatment naive CLL, and we've progressed two additional phase three trials as Lai will review. Importantly, we've reached our first registration milestone for Sonro. With a regulatory filing submitted in China. And we plan to submit our first global filing in the second half of this year. These filings mark the beginning of Sunro's evolution, in a potential game changing therapy across multiple B cell malignancies. We're the leading next generation of innovation in CLL with our first in class BTK CDAC program. Which has now dosed over 600 patients and continues to progress rapidly. We've reached an agreement with the FDA on a phase three dose, and we've already initiated our first phase three trial.

With plans to initiate another phase three trial against pirtobrutinib in the second half of the year. We continue to expect data from our potentially pivotal Phase II trial next year and pending positive results intend to complete global regulatory submission. Outside of heme, we continue to advance one of the broadest solid tumor pipelines in the industry. Our CDK four inhibitor continues to advance rapidly, with over three hundred patients enrolled, including over one hundred in just the past two months. Our b seven h four program, a key area of enthusiasm, has completed seven monotherapy cohorts promising signs of clinical activity. We enrolled the first patients in both of our clotting six CD three bispecific program for gynecological and other solid tumors and our second generation BCL two, metastatic breast cancer. And our PRNT-five inhibitor also entered the clinic in early Q1, marking another milestone in our targeted lung cancer therapy portfolio. This year, we anticipate more than 10 proof of concept readouts across our solid tumor pipeline. Each representing a potential near term value inflection point. These assets feature differentiated potentially first and or best in class profiles and have the potential to deliver transformational impact for both patients and shareholders.

Our internal clinical development team of 3,700 plus continues to demonstrate time, cost, and quality advantages. That are driving higher ROI for each r and d dollar spent. And we're routinely seeing proof of these advantages and programs in competitive settings like our BTK, CDAC, our BCL two, and our CDK four inhibitor, just to name a few. Moving to financial performance, we achieved a major milestone in q one. GAAP profitability for the first time. Aaron will provide more detail later in the call, but these strong quarterly results pace us on solid footing to deliver on our full year financial guidance. I'd like to close by sharing a few reflections on the external landscape as our industry continues to navigate in an increasingly challenging and complex global environment. I believe our unique model positions us exceptionally well to succeed in spite of today's challenges. Over the past fifteen years, we've built an organization from scratch that is technology enabled time and cost advantaged, and now vertically integrated. It was built not only to survive, but to thrive in a world with pricing pressure. In today's macro environment, a global manufacturing footprint and regional resilient are essential to ensuring product availability and operational continuity.

This has been a foundational principle of our operations across The US, Europe, China, and other key markets. We've realized this vision with action. Including most recently an $800,000,000 investment in our Hopewell, New Jersey manufacturing facility which opened in 2024. With the landscape around trade policies and tariffs, we'll continue to evolve Our commitment to regional manufacturing helps us mitigate potential risks and maintain reliable supply. Finally, I'm pleased to announce that the shareholders have approved our redomiciling to Switzerland from The Cayman Islands as well as our name change to BeiGene Medicines. Reflecting our continued evolution into a globally diversified oncology leader and our deepening ties to the world class Swiss biotech ecosystem. And with that, I'll pass it over to Xiaobing, to provide a global commercial update.

Thank you, John. Our global development strategy and the board trial design have resulted in the broadest label and a widespread coverage for Breckenza and Tibembro. We have achieved a significant global reach in a short period of time. And have now traded over 1,700,000 cancer patients with all therapies. This is the foundation. [indiscernible] foundational assets are well positioned to deliver meaningful benefit to patient worldwide. We have built the commercial infrastructure to successfully launch and scale across more than 80 markets. This strong foundation also positions us to fully leverage our global network to support internal clinic development and drive the successful commercialization of our pipeline. In the first quarter, global sales were $1,100,000,000 growing 49% from Q1 twenty twenty four. The U. S. Our largest market grew 60% Our strong Brokenza demand growth as Matt will discuss later. In addition, TIVENBRA was approved for frontline ESCC in The US during the quarter. China sales grew by 26% compared to the prior year period. With Tivembra and Brookings are sustaining their market leadership positions. Tivembra expanded NRDI coverage in frontline gastric and frontline small cell lung cancer and Amgen collaboration products also continued their strong momentum in the first quarter.

European experienced a 75% growth as we continue our launch for Brokynza and Tivimbra. We received reimbursement for Tivembra in Spain and early this week, Europe EU approval for TIVENBRA in frontline extensive stage small cell lung cancer We're encouraged by the growth perspective of the region for 2025. Rest of the world says totaled $32,000,000 in the first quarter. Growing 146% compared to the prior year This was primarily driven by expansion and new launches [indiscernible] MENA regions. Including notable progress in South Korea, Japan, Mexico and Brazil. While we're still in the early stage of commercialization in our rest of the world market, we expect them to be strong consistent contributor of future revenue growth and have us realize our mission to reach many more patients with improved access and affordability. I will now pass the presentation over to Matt to to provide The US commercial update Thanks, doctor Wu.

Moving to Burkansas US performance.

Q one US Burkynza sales reached 563,000,000, representing growth of 60% versus the prior year and establishing Brkenza as the market leader by revenue in the large and growing U. S. BTK market. Which grew 11% year over year. This is an important milestone that was reached just two years after our CLL launch. And while this strong performance underscores Perkins' continued momentum, the q one revenue reflects the typical seasonality seen across all products in the BTK class. As previously discussed on the q four update. For Kenza's q one net revenue and net revenue growth, was driven primarily by strong underlying demand. As you can see on this slide. Year over year demand growth was 54%. When compared to the first quarter of twenty twenty four. And 6% sequentially when compared to the fourth quarter. This steady trend of demand growth reflects our leadership in terms of new patient starts where we are the lead across all lines of therapy and indications, including both frontline and relapsedrefractory CLL. This momentum combined with the growing base of existing patients, underscores a solid foundation for on ongoing growth. We're confident in the underlying business fundamentals, and well positioned for strong performance in the second quarter and the rest of 2025.

Significant growth opportunities remain within the frontline CLL market. Where treatment success requires deep responses impressive and sustained PFS, and a strong safety profile. All areas in which Burkynza has consistently demonstrated proven advantages. Nearly half of all newly diagnosed CLL patients have one or more high risk features, including unmutated IGHV, deletion eleven q, and t p fifty three deletion 17p and even more have high risk comorbidities such as A fib. In this population, other BTK inhibitors and current fixed duration treatments are associated with poor outcomes. In the ALPINE trial, Burkynza became the only BTK to demonstrate superiority over ibrutinib, in a head to head trial. And in the high risk t p fifty three deletion seventeen p population subset of ALPINE. [indiscernible] at forty two and a half months median follow-up was fifty nine percent. Versus ibrutinib's PFS of thirty two percent. An impressive twenty seven percent higher. Burkynsia is the best in class option for all patients. Regardless of mutation or significant comorbidities. Given the challenges with current fixed duration regimens, and Burkina's best in class profile, We see additional opportunity for Burkynza monotherapy, to continue to take market share from these treatment options. And beyond expansion of BTK monotherapy, we believe that Brkenza plus Sonrel has the opportunity to deliver on the promise of fixed duration and expand its role in the treatment paradigm.

Similarly, our BTK CDAC has the potential to surpass the other existing treatment options and fulfill the unmet needs of patients with CLL. On that note, now over to you, Lai, Thanks, Matt. I would like to a few minutes to highlight key aspects of our portfolio. Starting with our hematology franchise. Our sales franchise is evolving quickly. We're relentlessly pursuing the best in class treatment options from frontline to late ones. Including both continuous and the fixed duration treatments. We believe that to advance the standard of care, the fundamental question or whether a potential medicine is better than the existing best and treatment options must be answered. The clinical trial needs to be designed accordingly. You can this you can see this in our past trials, including Alpine. And our current phase three trials for solo and our BT CDAC, which I will review today. Vocanza was designed from inception to provide twenty four seven inhibition of BTK in more disease relevant compartments. And to address efficacy challenges of ibrutinib. This led to a phase three victory over ibrutinib. In a direct comparison with last refractory CLL. Furthermore, its enhanced selectivity has resulted in improved tolerability in clinical settings.

Similarly, Sono exhibits higher potency and the selectivity compared to venetoclax. Offering potential advantages in efficacy and the safety. As supported by clinical data. With a shorter half life and no drug accumulation, Solu may allow for more patient friendly TLS monitoring. Which would serve as a key differentiator for Finitecracks. We believe that the vast majority of CLL patients will require only one single hospital visit for a solar ramp up of the Sanu Lehi. Our BDKC deck is the most advanced BDK degree that comes in the clinic. With preclinical properties indicating safety and efficacy benefits for patients.

Its novel mechanism of action offers distinct advantages over traditional inhibitors by overcoming and preventing emergent resistant mutations and disrupting scaffold functions. Next, I would like to discuss the fixed duration treatment landscape and the significance enhancing our leadership in CLL. To establish a compelling fixed duration therapy, you must achieve higher efficacy and the safety standards. In terms of efficacy, it must deliver extended PFS allowing patients to experience a general drug quality. This requires deep responses. Enabling doctors to feel confident that the risk of relapse is minimum when discontinued therapy. Which is measured by undetected UMRD. Furthermore, it should not present the end additional clinical meaning for safety concerns during the treatment period. All potential best in class fixed duration combination of Xanu with Sono has demonstrated deep MRD rate impressive and sustained PFS and an acceptable safety profiles. We are progressing rapidly with the development of this fixed duration combination therapy. In line with our standard practice, the SLASH zero three zero one trial was designed to demonstrate the PFS superiority of ACE plus over the current best standard of care in [indiscernible] in treatment naive CLL. This child completed enrollment in February within just fourteen months.

Marking a significant milestone for the program and showcasing strong interest from patients and clinicians and our clinical execution capabilities. In addition to treatment naive CLL, we're also advancing the development solo for [indiscernible] Which combines SONO with CD20. This is a true head to head trial designed to demonstrate the superior of sonar overfinite class. For mental cell lymphoma, a phase three trial has been initiated to evaluate the treatment effect of two years of Sonro combined with continuous Xanu in relapsedrefractory set. This trial will also serve as confirming trial for CELESTIAL two zero two, a single arm phase two study of monotherapy in relapsedrefractory mental cell lymphoma post the BTKi, which we plan to file globally for accelerated approval in the second half of this year if the results are positive. Moving on to our BTK CDAP. We presented a compelling early efficacy the safety data in a heavily pretreated population at ASH. As you can see here on this slide, the evolution of our data together with strong KOL feedback gave us confidence to initiate a head to head trial phase three study against the protobrutinib. The detail of the trial design is showing in this slide.

The first patient is expect to be enrolled in the second half of this year. We have met with FDA and obtained agreement on our dose for Phase three in CLL. I'm very excited to announce that our first Phase three study for the BTK CDAC Cadence three zero two, versus physician's choice in neuroblastoma factory cell patients had the first patient in this week. We have also started a multi cohort platform study to combine BTK CDAC with internal and external assets [indiscernible] Xanu, and the 20 bispecifics. These combinations have the potential to expand the treatment options for patients with B cell malignancies. Our solid tumor portfolio has evolved over the last two years with 19 new molecules in the clinic across three major tumor type lung, breast, gynecological cancers, and GI cancers. We have refined our portfolio to focus on targeted therapy utilizing modalities. Including ADCs, degraders, and the multi specifics. To deliver highly efficacious treatments for our patients. Our commitment to industry leading speed is evidenced by our fast to park strategy, which continue to drive the rapid development of these markets. I'd like to highlight several key pipeline value inflection points. During the presentation, I addressed some of our significant late stage milestones.

In addition, we had a successful phase two readout for Sonra in relapsedrefractory CLL and achieved the expedited NDA submission in China. Completing the process in an impressive eleven weeks from the data cutoff to the NDA acceptance. We anticipate our global filing in the last factory mental selling form mine in the second half of this year. Additional phase three pivotal trials for both Sono and our BTK CDAC will be initiated later this year. Turning to our early stage pipeline. We have several POC catalysts expected throughout the year. We'll provide more details regarding our innovative scientific advancements and the portfolio progression during our R and D Day on June 26. With that, 'd like to pass it over to Thanks, Lai.

We had a strong start to the year with first quarter twenty twenty five revenue of $1,100,000,000 compared to $752,000,000 in Q1 twenty twenty four. Revenue growth was 49%, with meaningful contributions across all of our key brands. These top line results are consistent with our communicated guidance expectations and set us up well for the balance of 2025. This quarter demonstrates our dual mandate in action. As we are driving significant top line growth with material operating leverage to support long term business sustainability. As a result of this focus, delivered positive GAAP operating profit and net income for the quarter. You can see the year over year improvement in GAAP and non GAAP operating profit measures of $272,000,000 and $286,000,000 respectively. And as a result of our value focused investment philosophy, we achieved a third consecutive quarter of positive operating cash flow, This is notable as the first quarter has a seasonally high use of working capital. When looking at our operating cash generation performance compared to Q1 twenty twenty four, we improved by $353,000,000 Sales of Brukinza totaled $792,000,000 in Q1, representing 62% growth as compared to Q1 twenty twenty four. Growth continues to be primarily driven by demand from our leading new patient share in The United States, coupled with year over year increased volume following a full year of use from patients who began treatment in 2024.

This is layered on top of the stable base of patients who remain on therapy from prior years given Brukinz's long duration of therapy. Growth contributions were seen across all geographies, including Europe, China and rest of world markets. TIMVIBRA sales of 171,000,000 resulted in 18% revenue growth when compared to Q1 twenty twenty four. Driven primarily by our leading market position in China. We're in the early stages of our commercial expansion in other markets. Amgen in licensed products were key contributors to performance coming in at 114,000,000 and grew 58% year over year. And finally, we are also seeing year over year growth contribution from collaboration revenue, given our global royalties for Indaltra. Now moving to the GAAP income statement. Product gross margin increased nearly two percentage points to 85% this quarter compared to 83% in Q1 twenty twenty four. This was largely due to favorable mix and cost of sales productivity for both TIVIMRA and Brukinza. Operating expenses totaled $941,000,000 representing growth of 6% as compared to Q1 twenty twenty four. Growth was seen in both SG and A and R and D as we continue to invest with discipline to support our commercial businesses, and our robust pipeline.

Note that Q1 twenty twenty four included $35,000,000 of business development expenses. Which should be considered when interpreting the period over period change. Taken together, our focus on top line growth with meaningful operating leverage led to our achievement of GAAP profitability for the quarter. Our non GAAP P and L includes adjustments for typical items, with a full reconciliation provided in the appendix. Focusing on the bottom line, non GAAP net income totaled $136,000,000 in Q1 twenty twenty five, an increase of $282,000,000 versus prior year. This equates to non GAAP earnings of $1.22 per ADS. Switching to guidance, Our full year 2025 guidance remains unchanged. We project revenue to be between 4,900,000,000.0 to 5,300,000,000.0 Movement in exchange rates, while volatile at the start of 2025, have largely offset and current rates are contemplated in this affirmed range. Our GAAP gross margin percentage is projected to be in the mid 80 percentile range benefiting from mix and production efficiencies. Operating expenses on a GAAP basis are anticipated to be between 4.1 and $4,400,000,000 Non GAAP operating expenses are expected to track with our GAAP guidance. With reconciling items remaining unchanged from existing practice. As we have demonstrated in the first quarter of twenty twenty five, we are committed to achieving full year GAAP operating income breakeven and generating positive cash flow from operations for the full year.

Recognizing uncertainty remains, our guidance in includes our estimates of the impacts of announced tariffs to our 2025 results. Do not expect a tariff impact associated with our partnered products. Our exposure has been mitigated by our significant investments and partnership to build a truly global production network, including our commitment to manufacturing in The United States for US supply of Brukinza to Vimbra and the commercialization of our pipeline assets. This includes our 42 acre Hopewell, New Jersey campus, which is currently being qualified for biologics production could be expanded to other modalities as needed to support our advancing pipeline. We will continue to take action to build supply chain resiliency to ensure patients around the world have uninterrupted access to our critically important life saving medicines. And with that, I will turn the call back to Dan.

Thanks, Aaron. We are now ready for q and a. I ask participants to limit themselves to one or two questions to ensure we have time to hear from as many attendees as possible. Operator, we are ready for the first question.

Thank you. If you would like to ask a question, please use the raised hand icon, which can be found at the bottom of the webinar application. When you are called on, please mute unmute your line and ask your question. We will now take a minute for the queue to assemble. Our first question comes from Andrew Berens at Leerink Partners. Please unmute your line and ask your question.

Hi. Thanks, and congrats on all the the progress I got a question on the CDK4 program. Can you just remind us how forty three three nine five differs from Pfizer's Otermo? And I know it's early where do you see the CDK four agents being used in HR positive breast cancer in terms of lines of therapy and and potential combination partners? And then maybe another question on Rekinza. Just wondering if you have any appetite to develop the drug beyond oncology Do you think there's a potential role in autoimmune diseases, and is this something that that you would consider doing yourself or or with a partner potentially?

Yeah. Thanks for the question. For the CDK four, our molecule was designed benchmarking against the the fighters [indiscernible] To be more potent as well as more selective Right now, we're still in the process of a dose escalation. We're moving this program very aggressively even in the the last one month or so, we have enrolled. Last couple of months, we have enrolled 100 patients. We still plan to move this forward into the phase III trials aggressively. The the current thinking around this molecule is to initiating a phase three trials in the second line settings in combination with search. So that's the plan. In addition to that, we're also contemplating the play in the earlier lines. As for your question related to the Burkina, outside of the oncology, we have a Phase III ongoing, which is in the membranous nephropathy. Which is the fourth point you mentioned about in the eye indication. Okay. Thank you. And do you have an oral SERD in in your portfolio that that has been disclosed?

We do not have a oral SERD.

Okay. Thank you.

Our next question comes from Yaron Werber. At Cowen and Company. Please unmute your line and ask your question.

Right. Thanks so much, and congrats on a a lot of pipeline progress.

Maybe may for Matt or Aaron, any can you give us a sense for Kinza in q one? Any any sense how much was the the weakness in the class related to the part d redesign And then for Tavimbra, is there any way you can split out sales in The US, Europe, sort of rest of world, and China? Thank you.

Do you wanna go ahead and start the Sure. Sure. This is Aaron. Thanks for the question you were in.

I mean, I would start, you know, without speaking to the broader industry. Obviously, Part d resigned to some has some impact. As it relates to pricing. You know, we've talked about a relatively stable net pricing environment for our company. You know, this is coming from a couple of factors. Of course, with the redesign, you know, as we look at our business, we do see some q one favorability driven by the redesign in part as a result of the elimination of the manufacturer liability for the coverage gap. As you know, that would largely be experienced earlier in the year. As patients work through the donut hole and then obviously manufacturers had the liability associated with that coverage gap. You know, for us, you know, with the redesign, we do benefit as we've spoken about from the specified small designation, which layers in our manufacturing liability. Over a five year period. So on balance, you know, as you think about q one, you get a little bit favorability given the lapping of the pricing in the base from 2024. And that's offset to a degree by the manufacturer liability on the D's redesign for us. Which will be consistent over the balance of this year.

So, other than that, Matt, anything you have? Maybe I'll add a little bit of commentary about Q1, related seasonality. I think that kind of goes hand in hand. With the Medicare Part D piece. Then I'll gladly, you know, address the US TIVENBRO component. Of the the question as well. And, we talked about some things back in the fourth quarter, related to what we anticipated in Q1 on seasonality There's a typical, you know, customer inventory build. In the fourth quarter with a drawdown that we then see in the in the first quarter. We disclosed about a $30,000,000 buy in. And then we also have noted, you know, one less shipping week in first quarter of this year. Than you know, than for other know, other typical quarters. So, you know, really in the first quarter, we typically see a slight drop in new starts due to changes in patient's insurance. And out of pocket resets and and other factors. So this first quarter was really no different than that. On the Tivembra US piece, we don't report separate breakouts for that, but we're very encouraged with the progress that's been made on Tovembra. In The US where we're very pleased to receive our frontline esophageal approval That was our third approval in The US.

Within a year. Coming after second line esophageal and frontline gastric And, of course, we were also very pleased to see listing in the NCCNET guidelines and also more recently, our alternative dosing q two w and q four w came in line, as well. So what we now see is initial experiences, patient starts, all in line with with launch expectations. And we'll see the second quarter really be the starting point for Tovembra in The US now that all those other factors have come into line?

If I could just maybe just follow-up on Brokenza, Sigrid approval now in EMA, yeah, EMA from Switzerland is is a big deal. How much inventory can they do? Can they supply The US market as well, or is there a chance that they'll have capacity to or or it sounds like you're talking to another manufacturer for The US. Any any update there?

Yeah. So thanks for the question. We are pleased with our approval for our second source of API from our Swiss supplier, as you mentioned. We are working to continue to broaden out our supply chain resiliency with, with sourcing from another supplier. In Spain. So that's a portion of our API usage. We've taken, a action to ensure we have significant stockpiles. Both for regular run, demand, but as well to have additional security. As it relates to our API stockpile. So we're we're we're confident in our position in that regard.

Thank you.

Our next question comes from Jessica Fye at JPMorgan. Please unmute your line and ask your question.

Hey, guys. Good morning. Thanks for taking my question. On the CDK four program, just to confirm, fair to think that efficacy data could come during your r and D day in late June? And can you maybe set the stage a little bit for what kind of data you'll share, I. E, there gonna be enough follow-up to get a look at you know, durability here, or should we mainly be expecting you know, more safety and response rates? And then also related to that program, can you just remind us where you are in terms of starting or enrolling a CDK four six naive cohort with that molecule?

Jessica, thanks for the question. In terms for the, for the data disclosure at R and D Day, we'll be mainly focused on the dose escalation cohorts. We're certainly including the efficacy data in addition to the safety, PK. But, however, as you noticed, this program moved very quickly, Actually, just in the last two months, we enrolled over 100 patients. So the durability side of it, as you can imagine, it will be limited. In term for, you know, this molecule's the second part of your question was about, CDK four six treatment. CDK four six nine treatment settings. So we actually have, enrolled patients already in that settings. We began to accumulate data in that setting. So we're eagerly waiting for that data to help us to make the decision in the front time.

And and will we see any of that at R and D Day?

That's too early to be disclosed at r and d day.

Okay.

Thank you.

Our next question comes from Reni Benjamin at Citizens. Please unmute your line and ask your question.

Hey, good morning, everyone. Thanks for taking the questions, and congratulations on all the progress. As you look at the 10 proof of concept readouts this year, can you maybe highlight maybe the you know, the the the top ones that you think could, you know, really drive your excitement as you as you move forward? And then separately, the Mangrove trial you mentioned has an interim analysis of the Phase III trial. Can you just provide an overview and just what your expectations are from that interim analysis? Thanks.

Yeah. Sensitive question. I got this question a lot. Where do I stop? There's so many really exciting programs We you know, we spread the progress. We actually anticipate the most molecules enter the clinic last year. We should expect the data. This year. I wouldn't say which one is my favorite. I actually like them all. In terms for the member of study, it's a event driven study. So we you know, while waiting you gotta wait in for the events to happen. So we hope that's what happened in the second half of this year.

Thank you. Next question comes from Michael Schmidt at Guggenheim Partners. Please unmute your line and ask your question.

Hey. Good morning. Thanks for taking our questions. I had a a follow-up on the the first line mantle cell lymphoma opportunity for Brukinza based on mangrove. Could you just help us understand the the size of that opportunity and you plan on submitting regulatory filings based on this interim data here in the second half? And then a question just longer term on the CLL market. You know, how how what is your view on how Brukinza is positioned longer term with the pirtobrutinib first line? Data reading out here later this year from Lilly? You know, what gives you confidence in in in Bruckensa's, you know, best in class market position long term in in CLL Thanks so much.

Yeah. I will probably start probably ask him to comment on commercial side of it. In terms for the first line, mango study, I just want to remind everybody about the study design. This is, we're using a chemo free regimen, which is a rituximab plus zanubrutinib. The control arm is BR. Is a little bit different from the ACO study, which is adding the a column on top of BR. We do believe this providing a really probably a ultimately if the trial is successful to the patients, which is chemo free. So this one thing was to highlight is in the frontal eye therapies, the treatment duration will be very long. So if it's successful, it does can further expand our marketing, the mental self. Later on, I'll ask Matt to comment how big the market is. Moving on to your com your question around Pluto side of it. The Pluto study in the front line is against the the BR. That's the first study. The second study was enrolling about one third of patients, which is in the treatment naive, but it's a mixed population also with the second line and the later line. The competitor there is a bunch of them.

So we don't we do not believe this presents significance threat to our book inside because the competitor is not the book inside.

Yep.

And I'll just briefly comment on Mandel Cell and then move over the period of related element of of the question. We you know, clearly see a reasonable size opportunity in in in nano cell and, in fact, you know, continue to see opportunities. For the BTK class, you know, in in that segment. And and also continue to have strong share position there. With regard to Pirto and the future outlook, you know, for for the class and for Rakenza, We fully expect to continue to maintain and expand market share our BTK therapy. Based on the PIERTO readouts recently, we think it's really unlikely to see significant shifts to earlier lines of therapy. We think that we've heard the competitor makes similar remarks you know, regarding sequence and And, you know, really believe that continuous BTK therapy is gonna continue to be the best option in those earlier lines of therapy. We also see that utilization is in line with that, and the and the Pure Toe is really being utilized in those later lines of therapy. Thank you. Our next comes from Zhi Chen. At Goldman Sachs. Please unmute your line and ask your question. Hey. Good morning, and thank you for taking my questions.

Two questions.

One on IRA, and the other one on expenses. So how do you see the potential impact of CalFront's getting to IRA this year? I know, with the new price gonna be effective in 2027. Also for your 13¢ IRA, what is gonna be your base case scenario? In in terms of expenses, we actually see you know, with a a major wave of approved concept data coming from the solid tumor pipeline. We believe there are gonna be a lot more trials being initiated and a lot more potential pivotal studies being initiated. So how should we see the trend of the R and D spending? In the first quarter, it's down a little bit quarter over quarter. But do you still have the flexibility in spending given you have the target of you know, profit making into in this year around potentially beyond 2025? Thank you.

Yeah. I guess I'll just start out with with with IRA and your question. Related to to Calpoints. We won't see Calpoint's IRA implications until 2026. We may see some indirect marketplace tied to impact, regardless. Of that price negotiation status. And we think that that's gonna be manageable Obviously, with respect to IMBRUVICA, We don't see it as a credible substitute for VIRKENSA. Due to safety and efficacy particularly given our ALPINE trial you know, showing head to head superiority and also the known cardiac toxicity profile for IMBRUVICA. We see substantial you know, differentiation there. Of course, know, later, with Caliprant, we see less cardiac issues than IMBRUVICA. But also questionable efficacy across multiple studies. And and clearly, know, I'd best see that as a poor subject to for Burkansas. So we continue to be pleased with our leadership position in new starts and relapsed and refractory and in frontline and are the most prescribed across the B cell malignancies. We we think that, know, continued strong market performance will be critical as we head into that that IRA time thing.

Great. Thank you. And with respect to our R and D investment, as you see in our 2025 guidance, we are investing significantly to rapidly advance our pipeline. You know, you did reference our dual mandate of driving you know, being a growth company but doing it in a sustainably sustainable way. And you see that in our operating results, not just this quarter, but in the preceding quarters as well. So we will continue to operate against that dual mandate of growth. With margin expansion. And we're committed to developing the pipeline. I think what we've talked about historically is, you know, having a strong type top line with disciplined investment still allows us to invest with growth against that emerging pipeline. We always speak to the fact that, you know, we we have a significant investment already, and we have a a pipeline that has had portfolio of late stage investments. You think about Tavimbra, You think about Brokenza. Think about our TIGIT program. Those were significant investments. Those are rolling over. And as we, they're being replaced by our investments in our current late stage pipeline and great opportunities and front of us with Sunro, with Sonro and then the greater that provides opportunity also with respect to our early stage program.

But we have talked about how BD is in our DNA. You know, we're fortunate to have such a robust pipeline. Talk Lai talked about how many favorites we do have. That provides a lot of optionality for us. These are all fully owned assets. So that you know, we're obviously, there's no shortage of interest in our pipeline. We're open to the optionality that affords. But given our strong balance sheet and our capital discipline, you know, we're not obligated to do anything. So we're really in a in a strong position. As it relates to advancing the pipeline and do and creating the the maximizing value, for our shareholders.

Thank you.

Our next comes from Kelly Shi at Jefferies. Please unmute your line and ask your question.

Hi, good morning. This is Clara on for Kelly. Thanks for taking our question and congrats the progress for the quarter. So for the Phase two data readout, for ciraptoploxacin refractory mental cell lymphoma in the second half of the year, and the BTK C that placed today are in 2026. Just wanted to clarify, what are the endpoints you and the regulatory agency are looking at to potentially support the registration? And, also, for the following of serendiplex in China, may you walk us through like, what what kind of the typical review timeline there. Thank you.

Yeah. Okay. Thanks for the question. For both Sono as well as PKCDA, those are typical single monotherapy Phase II studies. The primary endpoint in ROR and the DOR, this was post potential accelerated pooling. In term of for the the filing, we have already received the project review from the CDE. That's less on the CDE website. We're anticipating potential approval probably in the first half of next year.

Thank you.

Our next question comes from Gregory Renza at RBC Capital. Please unmute your line and ask your question.

Great. Hey. Hey. Good morning, John and team. Congrats on the progress, and and thanks for taking my my question. Maybe just on the Quest for Serial innovation and just around CLS and on the BTK CDAC. Just curious if you could comment on that relative positioning of the CDAC to routine BTKs in the longer term. One, what gives you confidence that 16,073 have the ability to beat curto in a head to head study? And secondly, certainly, with discussion around maybe some risks about using degraders earlier in treatment lines, in treatment settings, Just curious about potential mechanism resistance, how that could preclude other treatment options. Just curious on your view with respect to that sequencing. Thanks so much.

Yes.

Thanks for the question related to, you know, our confidence, our BTK degrader, I can tell you what that's increasing by day with more data coming in this really give us assurance this job is doing what it's supposed to do. To truly fully complete the grades BTK protein and our providing the patient sustained clinical benefits. What's with the additional data, you know, coming in and also our feedback from the KOLs really give us confidence to start this head to head trial. Versus portal. And this this child will be initiating the second half of this year. In term of utilizing the BTK degraded in the earlier line, I think that's your second question. We're getting data on that. We're opening a cohort in the treat BTKi naive patient population to test it out. This is definite MO different MOA versus traditional BeiGene theater. It's very early to say, you know, which one is better and what's the right sequence. So we've been doing the scientific experiment to test it but it's great to have the option of those traditional PD game capture as well as a PD beta grader. Addition to that, I just wanna finalize with the with [indiscernible] That give us a lot of different options to play in this space, which we think is very important.

We really want to provide the best option for patients not just in the front line, but also in the later lines.

That's great. Thank you very much. And if I may, an earlier question on BTK and PNM. I'm just curious how you're thinking about the I and I portfolio, certainly with the IRAK4. Is that an area that you want to expand upon as you think about internal and even external development? Thanks again, guys.

Yes. Thanks for that question. I didn't spend time to discuss our eye before you during the call. This is actually very exciting portfolio for We actually have a dozen of the program which we're developing in our space. Again, we're utilizing our, you know, Friday different modality trying to create the best, in class molecules as well as potentially first in class molecules. [indiscernible] We're super excited about this molecule. So far, the early data we have seen with this molecule [indiscernible] suggesting it has the best in class potential with its PK, with its level of the degradation. We believe we can achieve complete target operation at very low dose level. And we're also is eagerly anticipating our data in the tissue PD which should come in the second half of this year. But, well, as I mentioned, we also have other AI which we are really began to develop in the hopefully, you will see more coming from our pipeline in the next couple of years.

Thank you. Our next question comes from Sean Larman. At Morgan Stanley and Co. Please unmute your line and ask your question.

Morning, everyone. I hope you're all well. Some a simple benchmarking question to start. If you look at the the revenue reported by Venclexture, how would you size the opportunity for cerotaclax against that? You know, given potential better safety issues, you know, broadening improving efficacy, and and what other combination opportunities there might be.

Yeah. Thanks for the question. You know, that [indiscernible] [indiscernible] tons of competition. In the b c r two field, truly, there's really two molecules. One is venetoclax. One is like, We actually, very excited about the portfolio of the profile of our sponsored packs. It's, much more potent. And also more selective. Right now, you we are seeing that in a different indication with the response rate, with duration of response. This is why it give us the confidence to start in more than just one patch to patch trial. The first trial we mentioned, was our semester. So one we already finished enrollment. This is CS regimen versus [indiscernible] And we are very excited about the second trial as well, which is in the refractory cell setting. To, testing [indiscernible] c d 20 combination setting, but this is truly head to head trial. We believe with those two trials can really establish, so and as the potentially the best in class PCR two. This is critical. But in addition to that, I just wanna mention, we are also the indications which venetoclax really had a success. That's including multiple myeloma. We cannot talk about that trial for a while now, but that trial is, moving along, very nicely.

We're anticipating reporting more data later this year. Now I'll hand over to Matt.

Yeah. I can just offer some commentary on the you know, the market opportunity and you know, we currently see the opportunity for a BCL two. And a CV 20 to be about about a quarter. Of of that frontline opportunity in CLL. And and we've said a number of times, that we think that there's you know, really three necessary components for for success, and in particular, with fixed duration. That's deep response and undetectable MRD, long PFS, and and strong safety. And more recently, we've seen some of the fixed duration regimens fail to heat that high bar. For some of the reasons that Lai has outlined, know, we're very confident that there'll be opportunities with, Zanu and Sanro to to meet that high bar and then ultimately lead to some expansion. Of the use of the b c l twos and c d twenties in, you know, in that setting. So you know, that that's a possibility. And then, clearly, we see Xynu and Sonro as being the real driver for expansion. In, you know, in that setting.

Thank you. And and one more quick one, if I may. More on the commercial side. But historically, when you do benchmarking against Brukinza revenue against peers across Europe, you you seem sort of underweight. If you like. But I'm just wondering if you there's good momentum, it appears, in this quarter you think you've got the investment about right in terms of sales to to really grow that European revenue? Or it just sort of map that map that out for me a little bit would be awesome.

Mhmm. Yeah. You European business is growing nicely, and you have seen that we grow, so 75% on the Burkina side. And, increasingly and we also increasingly we have more new patient to share so far. And in terms of, tilumbra and we get a new product launched in Germany, in Austria, Spain, and also some other countries like Switzerland and no Norway. And we also got a reimbursement under three reimbursement countries [indiscernible] the launch activity is on track. In the rest of the world, and, you can say, [indiscernible] And we have also launched [indiscernible] [indiscernible] recently and we also got approval of Team Enver in multiple countries in Brazil, in South Korea, reimbursement, Australia, [indiscernible] and this is also, we see significant progress in Thank you.

Thank you. Our final question comes from Yigal Nochomovitz from Citigroup.

Please unmute your line and ask your question.

Hi. Great. Thank you very much. I had a few questions. First, on the zan Sonro plus Xanu pricing. I know it's early, but I'd like to get your early thoughts if you're expecting that to be price neutral with Brutinza with the idea to take more share with a better profile. Or possibly a premium And then you talked a lot about supply chain resiliency, and you mentioned the the sourcing of API. Switzerland and Spain. Obviously, you have the film finish in The United States. I'm wondering if there's some long range plans to additionally introduce an API supply within The United States. And then finally, John, you talked a lot about resiliency. I'm curious about geographic resiliency, specifically with respect to R and D. With the redomicile in Switzerland, do you expect to move more of the core R and D outside of China to Switzerland as well as as well as US? You very much.

So thanks for the question, Yigal. So I'll take the first couple and then hand it over to John. You know, it's way too early to talk pricing. With respect to our pipeline assets. All I'll say is we're really confident in the profiles that these assets, have in front of them, and we'll price them accordingly relative to the value that they're creating. Patients. With respect to, supply chain resiliency, yes, we're very, we're very enthused by the efforts we've taken in the past to ensure that we have supply and resilience for patients all around the world. Obviously, we are, monitoring all the activity that's happening in the environment. And we'll be sure that we take measures to proactively ensure that supply for US patients, but really importantly, patients everywhere around the globe. So [indiscernible] Yeah. We're as you mentioned, we're excited about things, from a global perspective. And I think the organization is always in this, like, global expansion mode. Last quarter, I think you heard us talk about you know, opening operations in South Africa, for example. You know, today, the management team is sitting here in our sand Carlos you know, office and r and d center.

And, you know, excited to be yeah, interviewed and recruiting people here for the r and d perspective too. So, I just think it's, inevitable expansion process as we try to work globally with everyone and know, from a research, from a clinical, and getting great medicines to patients for something.

Thank you.

Thanks.

There are no further questions. I will turn the call over to John Euler for closing remarks. Thanks so much.

Think our first quarter execution across the key priorities really sets us strong foundation for 2025, and I'm really looking forward to sharing more updates and milestones with, all of you throughout the year. So thanks so much for joining us today and taking your time and energy and for the very thoughtful thrust. And have a wonderful day.