Q4 2025 BeOne Medicines AG Earnings Call

[Company Representative] (BeOne Medicines): CMO for Solid Tumors, and Amit Agarwal, CMO for Hematology. I'll now pass the call over to John. John?

Dan Maller: CMO for Solid Tumors, and Amit Agarwal, CMO for Hematology. I'll now pass the call over to John. John?

Speaker #1: CMO for solid tumors, and I'm at our bar wall, CMO for hematology. I'll now pass the call over to John. John?

Speaker #2: Thanks, Dan, and thank you, everyone, for joining us today. Q4 marked another solid quarter of execution, and I really strong finish to the year.

[Company Representative] (BeOne Medicines): Thanks, Dan, and thank you everyone for joining us today. Q4 marked another solid quarter of execution and a really strong finish to the year. What a year it was! 2025 certainly lived up to its promise as a year of inflection for BeOne. From a financial perspective, we delivered on our commitments, achieving significant product revenue growth, GAAP profitability, and meaningful cash flow generation. In 2025, our foundational BTK inhibitor, BRUKINSA, became number one, both in the US and globally. As you can see on this slide, the gap between BRUKINSA and the competition is widening. That's not just a commercial achievement, it's a scientific one. BRUKINSA's long-term data have consistently raised the bar in CLL, setting a new standard for efficacy and safety.

John Oyler: Thanks, Dan, and thank you everyone for joining us today. Q4 marked another solid quarter of execution and a really strong finish to the year. What a year it was! 2025 certainly lived up to its promise as a year of inflection for BeOne. From a financial perspective, we delivered on our commitments, achieving significant product revenue growth, GAAP profitability, and meaningful cash flow generation. In 2025, our foundational BTK inhibitor, BRUKINSA, became number one, both in the US and globally. As you can see on this slide, the gap between BRUKINSA and the competition is widening. That's not just a commercial achievement, it's a scientific one. BRUKINSA's long-term data have consistently raised the bar in CLL, setting a new standard for efficacy and safety.

Speaker #2: And what a year it was. 2025 certainly lived up to its promise as a year of inflection for B1. From a financial perspective, we delivered on our commitments, achieving significant product revenue growth, gap profitability, and meaningful cash flow generation.

Speaker #2: In 2025, our foundational BTK inhibitor, Brukinza, became number one both in the U.S. and globally. And as you can see on this slide, the gap between Brukinza and the competition is widening.

Speaker #2: And that's not just a commercial achievement; it's a scientific one. Brukinza's long-term data have consistently raised the bar in CLL, setting a new standard for efficacy and safety.

Speaker #2: These results are reinforced by an expanding body of clinical and real-world evidence, all of which support the program's best-in-class hypothesis. CLL is a $12 billion in growing market due to remarkable therapeutic innovation, an improvement in patient outcomes over the past 15 years.

[Company Representative] (BeOne Medicines): These results are reinforced by an expanding body of clinical and real-world evidence, all of which support the program's best-in-class hypothesis. CLL is a $12 billion and growing market due to remarkable therapeutic innovation and improvement in patient outcomes over the past 15 years, but it wasn't always that way. As recently as the mid-2000s, patients with CLL received fixed-duration chemo, and outcomes were quite poor. In fact, the median progression-free survival for patients taking chlorambucil was less than 1 year. In 2008, bendamustine was approved and used in combination with rituximab, and the use became widespread, providing substantial benefit over the first chemo-based regimens. 6-year progression-free survival increased to 32%, which was better, but still not great. The FDA approval of ibrutinib in 2016 marked the first chemo-free option and a seminal innovation for patients.

John Oyler: These results are reinforced by an expanding body of clinical and real-world evidence, all of which support the program's best-in-class hypothesis. CLL is a $12 billion and growing market due to remarkable therapeutic innovation and improvement in patient outcomes over the past 15 years, but it wasn't always that way. As recently as the mid-2000s, patients with CLL received fixed-duration chemo, and outcomes were quite poor. In fact, the median progression-free survival for patients taking chlorambucil was less than 1 year. In 2008, bendamustine was approved and used in combination with rituximab, and the use became widespread, providing substantial benefit over the first chemo-based regimens. 6-year progression-free survival increased to 32%, which was better, but still not great. The FDA approval of ibrutinib in 2016 marked the first chemo-free option and a seminal innovation for patients.

Speaker #2: But it wasn't always that way. As recently as the mid-2000s, patients with CLL received fixed-duration chemo, an outcome that was quite poor. In fact, the median progression-free survival for patients taking chlorambucil was less than one year.

Speaker #2: In 2008, bendamustine was approved and used in combination with rituximab, and the use became widespread. Providing substantial benefit over the first chemo-based regimens. Six-year progression-free survival increased to 32%, which was better but still not great.

Speaker #2: The FDA approval of ibrutinib in 2016 marked the first chemo-free option and a seminal innovation for patients. Anchored by data that were superior to chemo, the field switched away from fixed-duration approaches to continuous BTK inhibition, why?

[Company Representative] (BeOne Medicines): Anchored by data that were superior to chemo, the field switched away from fixed-duration approaches to continuous BTK inhibition. Why? It provided the best long-term outcomes for patients. You can see ibrutinib's six-year progression-free survival and overall survival of approximately 61% and 77% respectively. At the same time, the field was developing new fixed-duration treatments that were enabled by the discovery of BCL-2 inhibition and the approval of venetoclax. These VEN-based approaches greatly improved upon historic chemo-based regimens, and they began to approach the long-term benefits provided by the two continuous BTKIs, albeit with approximately 10% delta in six-year progression-free survival. However, the VI regimen was not approved by the FDA, and the addition of obinutuzumab to VEN has significant safety challenges, which I'm gonna touch on later. As good as continuous use ibrutinib was, the molecule was not optimized for potency or selectivity.

John Oyler: Anchored by data that were superior to chemo, the field switched away from fixed-duration approaches to continuous BTK inhibition. Why? It provided the best long-term outcomes for patients. You can see ibrutinib's six-year progression-free survival and overall survival of approximately 61% and 77% respectively. At the same time, the field was developing new fixed-duration treatments that were enabled by the discovery of BCL-2 inhibition and the approval of venetoclax. These VEN-based approaches greatly improved upon historic chemo-based regimens, and they began to approach the long-term benefits provided by the two continuous BTKIs, albeit with approximately 10% delta in six-year progression-free survival. However, the VI regimen was not approved by the FDA, and the addition of obinutuzumab to VEN has significant safety challenges, which I'm gonna touch on later. As good as continuous use ibrutinib was, the molecule was not optimized for potency or selectivity.

Speaker #2: Because it provided the best long-term outcomes for patients. You can see ibrutinib's six-year progression-free survival and overall survival of approximately 61% and 77%, respectively.

Speaker #2: At the same time, the field was developing new fixed-duration treatments. They were enabled by the discovery of BCL2 inhibition and the approval of venetoclax.

Speaker #2: These ven-based approaches greatly improved upon historic chemo-based regimens, and they began to approach the long-term benefits provided by the two continuous BTKIs, albeit with approximately a 10% delta in six-year progression-free survival.

Speaker #2: However, the VI regimen was not approved by the FDA, and the addition of obinutuzumab to VEN has significant safety challenges, which I'm going to touch on later.

Speaker #2: As good as continuous use of ibrutinib was, the molecule was not optimized for potency or selectivity. The second approved BTK inhibitor, acalibrutinib, was designed to be more selective than ibrutinib, and to have a very short half-life of roughly one hour.

[Company Representative] (BeOne Medicines): The second approved BTK inhibitor, acalabrutinib, was designed to be more selective than ibrutinib and to have a very short half-life of roughly 1 hour, with the hypothesis that these changes would translate to a more favorable safety profile, including fewer cardiac adverse events. In that respect, acalab achieved its goal, demonstrating statistically significant improvement in AFib in the ELEVATE-RR study. However, in that same study, acalab demonstrated non-inferior PFS compared to ibrutinib. As shown on this scatter plot, acalab's 6-year progression-free survival and overall survival of 62% and 76% in treatment-naive CLL is nearly superimposable on ibrutinib. Innovation never stops. The bar set by the first 2 continuous treatments would be raised yet again by a differentiated foundational medicine. Enter BRUKINSA. BRUKINSA was designed from inception to be both more potent and more selective than ibrutinib, with complete 24/7 target coverage.

John Oyler: The second approved BTK inhibitor, acalabrutinib, was designed to be more selective than ibrutinib and to have a very short half-life of roughly 1 hour, with the hypothesis that these changes would translate to a more favorable safety profile, including fewer cardiac adverse events. In that respect, acalab achieved its goal, demonstrating statistically significant improvement in AFib in the ELEVATE-RR study. However, in that same study, acalab demonstrated non-inferior PFS compared to ibrutinib. As shown on this scatter plot, acalab's 6-year progression-free survival and overall survival of 62% and 76% in treatment-naive CLL is nearly superimposable on ibrutinib. Innovation never stops. The bar set by the first 2 continuous treatments would be raised yet again by a differentiated foundational medicine. Enter BRUKINSA. BRUKINSA was designed from inception to be both more potent and more selective than ibrutinib, with complete 24/7 target coverage.

Speaker #2: With the hypothesis that these changes would translate to a more favorable safety profile including fewer cardiac adverse events. And in that respect, acali achieved its goal, demonstrating statistically significant improvement in AFib in the Elevate RR study.

Speaker #2: However, in that same study, acali demonstrated non-inferior PFS compared to ibrutinib. As shown on this scatter plot, acali's six-year progression-free survival and overall survival of 62% and 76% in treatment naive CLL is nearly superimposable on ibrutinib.

Speaker #2: But innovation never stops. The bar set by the first two continuous treatments would be raised yet again. By a differentiated foundational medicine. Enter Brukinza.

Speaker #2: Brukinza was designed from inception to be both more potent and more selective than ibrutinib, with complete 24/7 target coverage. We took that preclinical hypothesis into the clinic where, in head-to-head global phase three trial, Brukinza demonstrated superior efficacy to ibrutinib and a more favorable safety profile.

[Company Representative] (BeOne Medicines): We took that preclinical hypothesis into the clinic, where in head-to-head global phase III trial, BRUKINSA demonstrated superior efficacy to ibrutinib and a more favorable safety profile. This includes statistically significant improvement in AFib. At ASH 2025, BRUKINSA set a new bar for long-term patient outcomes. Here we can see six-year progression-free survival and overall survival of 74% and 84%. Adjusting these for COVID, those are 77% and 87% respectively. Now, I really appreciate you bearing with me, as I know I've spent a lot of time on this slide, but the data, as you can see here, is really important. These data clearly establish BRUKINSA as a foundational standard against which all current and all future regimens must be compared, and the long-term outcomes that patients and physicians should expect and demand.

John Oyler: We took that preclinical hypothesis into the clinic, where in head-to-head global phase III trial, BRUKINSA demonstrated superior efficacy to ibrutinib and a more favorable safety profile. This includes statistically significant improvement in AFib. At ASH 2025, BRUKINSA set a new bar for long-term patient outcomes. Here we can see six-year progression-free survival and overall survival of 74% and 84%. Adjusting these for COVID, those are 77% and 87% respectively. Now, I really appreciate you bearing with me, as I know I've spent a lot of time on this slide, but the data, as you can see here, is really important. These data clearly establish BRUKINSA as a foundational standard against which all current and all future regimens must be compared, and the long-term outcomes that patients and physicians should expect and demand.

Speaker #2: And this includes statistically significant improvement in AFib. And at ASH 2025, Brukinza set a new bar for long-term patient outcomes. Here, we can see six-year progression-free survival and overall survival of 74% and 84%.

Speaker #2: And adjusting these for COVID, those are 77% and 87%, respectively. Now, I really appreciate you bearing with me as I know I've spent a lot of time on this slide, but the data as you can see here is really important.

Speaker #2: These data clearly establish Brukinza as a foundational standard against which all current and all future regimens must be compared. And the long-term outcomes that patients and physicians should expect and demand.

Speaker #2: At B1, we believe that true innovation comes from improving upon the best. Brukinza did just that when it demonstrated superiority in terms of safety and efficacy over ibrutinib.

[Company Representative] (BeOne Medicines): At BeOne, we believe that true innovation comes from improving upon the best. BRUKINSA did just that when it demonstrated superiority in terms of safety and efficacy over ibrutinib. No other BTK inhibitor can make that claim. Here we see the Kaplan-Meier curves from head-to-head trials of BRUKINSA and other BTK inhibitors versus ibrutinib in relapsed refractory BTK, naive CLL patients, and this is as assessed by Independent Review Committee or IRC. In all of these studies, the IRC-assessed PFS is the predefined key secondary endpoint to demonstrate superiority over ibrutinib. In the ALPINE trial, BRUKINSA showed the greatest early separation from ibrutinib and remains separated with a hazard ratio of 0.69 and a p-value of 0.001, demonstrating statistical superiority on PFS. We presented longer-term follow-up data from that study at ASH just a few months ago.

John Oyler: At BeOne, we believe that true innovation comes from improving upon the best. BRUKINSA did just that when it demonstrated superiority in terms of safety and efficacy over ibrutinib. No other BTK inhibitor can make that claim. Here we see the Kaplan-Meier curves from head-to-head trials of BRUKINSA and other BTK inhibitors versus ibrutinib in relapsed refractory BTK, naive CLL patients, and this is as assessed by Independent Review Committee or IRC. In all of these studies, the IRC-assessed PFS is the predefined key secondary endpoint to demonstrate superiority over ibrutinib. In the ALPINE trial, BRUKINSA showed the greatest early separation from ibrutinib and remains separated with a hazard ratio of 0.69 and a p-value of 0.001, demonstrating statistical superiority on PFS. We presented longer-term follow-up data from that study at ASH just a few months ago.

Speaker #2: No other BTK inhibitor can make that claim. Here we see the Kaplan-Meyer curves from head-to-head trials of Brukinza and other BTK inhibitors versus ibrutinib in relapsed refractory BTK naive CLL patients.

Speaker #2: And this is as assessed by independent review committee, or IRC. In all of these studies, the IRC assessed PFS is the predefined key secondary endpoint to demonstrate superiority over ibrutinib.

Speaker #2: In the Alpine trial, Brukinza showed the greatest early separation from ibrutinib and remained separated, with a hazard ratio of 0.69 and a p-value of 0.001, demonstrating statistical superiority on PFS.

Speaker #2: We presented longer-term follow-up data from that study at ASH just a few months ago. In the Elevate RR study, acali showed early PFS separation from ibrutinib, albeit less than Brukinza.

[Company Representative] (BeOne Medicines): In the ELEVATE-RR study, Acala showed early PFS separation from ibrutinib, albeit less than BRUKINSA, but that early separation was not sustained. As you can see in the middle chart, Acala crossed over and became numerically worse than ibrutinib at roughly 33 months. ELEVATE-RR ultimately reported a hazard ratio of 1. This brings me to pirtobrutinib, a non-covalent BTK inhibitor, which recently reported data from its head-to-head trial against ibrutinib in CLL. On the right, we see the curves from relapsed refractory BTKI naive cohort of BRUIN CLL-314, which comprised two-thirds of the enrolled patients in that trial. You can see that Perto, with only 18 months of follow-up, shows the least early separation versus ibrutinib, with a hazard ratio of 0.845 and a p-value of 0.4102.

John Oyler: In the ELEVATE-RR study, Acala showed early PFS separation from ibrutinib, albeit less than BRUKINSA, but that early separation was not sustained. As you can see in the middle chart, Acala crossed over and became numerically worse than ibrutinib at roughly 33 months. ELEVATE-RR ultimately reported a hazard ratio of 1. This brings me to pirtobrutinib, a non-covalent BTK inhibitor, which recently reported data from its head-to-head trial against ibrutinib in CLL. On the right, we see the curves from relapsed refractory BTKI naive cohort of BRUIN CLL-314, which comprised two-thirds of the enrolled patients in that trial. You can see that Perto, with only 18 months of follow-up, shows the least early separation versus ibrutinib, with a hazard ratio of 0.845 and a p-value of 0.4102.

Speaker #2: But that early separation was not sustained. As you can see in the middle chart, acali crossed over and became numerically worse than ibrutinib. At roughly 33 months.

Speaker #2: Elevate RR ultimately reported a hazard ratio of 1. And this brings me to pertibrutinib, a non-covalent BTK inhibitor, which recently reported data from its head-to-head trial against ibrutinib in CLL.

Speaker #2: On the right, we see the curves from the relapsed refractory BTKi-naive cohort of BRUIN-314, which comprised two-thirds of the enrolled patients in that trial.

Speaker #2: You can see that perti, with only 18 months of follow-up, shows the least early separation versus ibrutinib, with a hazard ratio of 0.845 and a p-value of 0.4102.

Speaker #2: We need to see much longer follow-up from Bruin 314 based on the minimal early separation in these short-term curves, and perti may face an uphill battle in showing statistical superiority to ibrutinib in PFS.

[Company Representative] (BeOne Medicines): We need to see much longer follow-up from BRUIN CLL-314 based on the minimal early separation in these short-term curves. pirtobrutinib may face an uphill battle in showing statistical superiority to ibrutinib in PFS. Now, if you've learned anything about BeOne Medicines over our 15 years of existence, it's that we're never satisfied with the status quo. Despite the incredible progress the industry has made, it's hard not to dream about the next chapter of CLL innovation. We think it's time to start talking about a cure. With that, we propose 3 aspirational goals for the next wave of innovation in CLL. The first one is an obvious one, life expectancy equal to that of the general population, matched for geography and age, for any patient diagnosed with CLL.

John Oyler: We need to see much longer follow-up from BRUIN CLL-314 based on the minimal early separation in these short-term curves. pirtobrutinib may face an uphill battle in showing statistical superiority to ibrutinib in PFS. Now, if you've learned anything about BeOne Medicines over our 15 years of existence, it's that we're never satisfied with the status quo. Despite the incredible progress the industry has made, it's hard not to dream about the next chapter of CLL innovation. We think it's time to start talking about a cure. With that, we propose 3 aspirational goals for the next wave of innovation in CLL. The first one is an obvious one, life expectancy equal to that of the general population, matched for geography and age, for any patient diagnosed with CLL.

Speaker #2: Now, if you've learned anything about BeOne Medicines over our 15 years of existence, it's that we're never satisfied with the status quo. And despite the incredible progress the industry has made, it's hard not to dream about the next chapter of CLL innovation.

Speaker #2: And we think it's time to start talking about a cure. And with that, we propose three aspirational goals for the next wave of innovation in CLL.

Speaker #2: The first one is an obvious one. Life expectancy equal to that of the general population, match for geography and age, for any patient diagnosed with CLL.

Speaker #2: Second, for patients who prefer a time-limited therapy any regimen must deliver long-term outcomes that are at least as good as the best continuous treatment available.

[Company Representative] (BeOne Medicines): Second, for patients who prefer a time-limited therapy, any regimen must deliver long-term outcomes that are at least as good as the best continuous treatment available. Finally, any treatment designed to offer long-term life expectancy must also deliver quality of life, ease of use, and convenience. Applying these aspirations to the scatter plot clearly implies the need for further improvements on what's currently available. We do believe that BeOne is the only company with the foundational assets in our CLL portfolio and pipeline to take us there. The next chapter in CLL innovation is going to come from options that address the unmet needs and deliver the best long-term outcomes for patients. What about fixed duration? There's a clear desire from some patients and physicians for fixed-duration options that provide a break from treatment.

John Oyler: Second, for patients who prefer a time-limited therapy, any regimen must deliver long-term outcomes that are at least as good as the best continuous treatment available. Finally, any treatment designed to offer long-term life expectancy must also deliver quality of life, ease of use, and convenience. Applying these aspirations to the scatter plot clearly implies the need for further improvements on what's currently available. We do believe that BeOne is the only company with the foundational assets in our CLL portfolio and pipeline to take us there. The next chapter in CLL innovation is going to come from options that address the unmet needs and deliver the best long-term outcomes for patients. What about fixed duration? There's a clear desire from some patients and physicians for fixed-duration options that provide a break from treatment.

Speaker #2: And finally, any treatment designed to offer long-term life expectancy must also deliver quality of life and ease of use and convenience. Applying these aspirations to the scatter plot, clearly implies the need for further improvements on what's currently available.

Speaker #2: And we do believe that B1 is the only company with the foundational assets in our CLL portfolio and pipeline to take us there. The next chapter of CLL innovation is going to come from options that address the unmet needs and deliver the best long-term outcomes for patients.

Speaker #2: So what about fixed duration? There's a clear desire from some patients and physicians for fixed duration options. That provide a break from treatment. For fixed duration to change the treatment paradigm it must elicit a deep response demonstrates sustained progression-free survival be safe with only minimal affection risk over continuous BTKI and be convenient to administer.

[Company Representative] (BeOne Medicines): For fixed duration to change the treatment paradigm, it must elicit a deep response, demonstrate sustained progression-free survival, be safe with only minimal affection risk over continuous BTKI, and be convenient to administer. We would argue it must be compared to the foundational CLL medicine, BRUKINSA. Naturally, patients want to be off treatment, but just as they want to know what they're gaining, every patient also wants to know what they're giving up. If that's overall survival, it's important that this is considered in the shared decision-making. How do current fixed-duration options compare to BRUKINSA? In our opinion, not very well. Existing VEN-based BTKI regimens have liabilities that have limited their uptake and approval.

John Oyler: For fixed duration to change the treatment paradigm, it must elicit a deep response, demonstrate sustained progression-free survival, be safe with only minimal affection risk over continuous BTKI, and be convenient to administer. We would argue it must be compared to the foundational CLL medicine, BRUKINSA. Naturally, patients want to be off treatment, but just as they want to know what they're gaining, every patient also wants to know what they're giving up. If that's overall survival, it's important that this is considered in the shared decision-making. How do current fixed-duration options compare to BRUKINSA? In our opinion, not very well. Existing VEN-based BTKI regimens have liabilities that have limited their uptake and approval.

Speaker #2: And we would argue it must be compared to the foundational CLL medicine Brukinza. Naturally, patients want to be off treatment. But just as they want to know what they're gaining, every patient also wants to know what they're giving up.

Speaker #2: If that's overall survival, it's important that this is considered in the shared decision-making. So how do current fixed duration options compare to Brukinza? In our opinion, not very well.

Speaker #2: Existing ven-based BTKI regimens have liabilities that have limited their uptake and approval. These include underwhelming efficacy as seen in the amplified trial, where the AV combination had an inferior depth of response compared to chemo.

[Company Representative] (BeOne Medicines): These include underwhelming efficacy, as seen in the AMPLIFY trial, where the AV combination had an inferior depth of response compared to chemo, demonstrating a undetectable MRD of only 34%, despite AMPLIFY enrolling a young, fit, and low-risk frontline population. In fact, AV's PFS at 3 years follow-up was roughly the same as BRUKINSA's at 6 years. It's quite noteworthy that we haven't seen an updated cut from AMPLIFY for nearly 2 years. Similarly, with respect to safety, AV and VI have limitations due to VEN, a less potent and less selective first-generation BCL-2 inhibitor. In terms of convenience, the low depth of response for AV may result in most patients having to be treated for far longer than one year to reach an undetectable MRD.

John Oyler: These include underwhelming efficacy, as seen in the AMPLIFY trial, where the AV combination had an inferior depth of response compared to chemo, demonstrating a undetectable MRD of only 34%, despite AMPLIFY enrolling a young, fit, and low-risk frontline population. In fact, AV's PFS at 3 years follow-up was roughly the same as BRUKINSA's at 6 years. It's quite noteworthy that we haven't seen an updated cut from AMPLIFY for nearly 2 years. Similarly, with respect to safety, AV and VI have limitations due to VEN, a less potent and less selective first-generation BCL-2 inhibitor. In terms of convenience, the low depth of response for AV may result in most patients having to be treated for far longer than one year to reach an undetectable MRD.

Speaker #2: Demonstrating an undetectable MRD of only 34%. Despite amplify enrolling a young, fit, and low-risk frontline population. In fact, AVs PFS at three years follow-up was roughly the same as Brukinza's at six years.

Speaker #2: And it's quite noteworthy that we haven't seen an updated cut from amplify for nearly two years. And similarly, with respect to safety, AV and VI have limitations due to ven.

Speaker #2: A less potent and less selective first-generation BCL2 inhibitor. In terms of convenience, the low depth of response for AV may result most patients having to be treated for far longer than one year to reach an undetectable requires cumbersome patient monitoring due to its long half-life and TLS risk, which calls into question the convenience benefit of this all-oral regimen.

[Company Representative] (BeOne Medicines): In addition, VEN requires cumbersome patient monitoring due to its long half-life and TLS risk, which calls into question the convenience benefit of this all-oral regimen. At the highest level, the primary benefit of fixed-duration therapy is the treatment-free interval, during which patients are not exposed to the potential side effects of ongoing therapy. In CLL, this means avoiding the agents that suppress rapid B-cell expansion, which allow for immune recovery and a reduced risk of infection. Fixed-duration therapies should lower infection risk over time, not raise it. The CLL17 trial studied fixed-duration VO and VI versus continuous ibrutinib, and it was presented at ASH a few months ago. The chart on the left shows the CLL17 trial data, which tells a clear and quite concerning story.

John Oyler: In addition, VEN requires cumbersome patient monitoring due to its long half-life and TLS risk, which calls into question the convenience benefit of this all-oral regimen. At the highest level, the primary benefit of fixed-duration therapy is the treatment-free interval, during which patients are not exposed to the potential side effects of ongoing therapy. In CLL, this means avoiding the agents that suppress rapid B-cell expansion, which allow for immune recovery and a reduced risk of infection. Fixed-duration therapies should lower infection risk over time, not raise it. The CLL17 trial studied fixed-duration VO and VI versus continuous ibrutinib, and it was presented at ASH a few months ago. The chart on the left shows the CLL17 trial data, which tells a clear and quite concerning story.

Speaker #2: At the highest level, the primary benefit of fixed duration therapy is the treatment-free interval. During which patients are not exposed to the potential side effects of ongoing therapy.

Speaker #2: In CLL, this means avoiding the agents that suppress rapid B-cell expansion. Which allow for immune recovery and a reduced risk of infection. So fixed duration therapies should lower infection risk over time.

Speaker #2: Not raise it. The CLL-17 trial studied fixed duration VO and VI versus continuous ibrutinib. And it was presented at ASH a few months ago.

Speaker #2: The chart on the left shows the CLL-17 trial data, which quite concerning story. First, after one year of VO, severe infections continue to climb for three years while the patient was off treatment as seen in blue.

[Company Representative] (BeOne Medicines): First, after 1 year of VO, severe infections continued to climb for 3 years while the patient was off treatment, as seen in blue. These infections are serious, often requiring hospitalization and IV antibiotics. Second, even after 4 years, severe infections were still higher with VO than with continuous ibrutinib, despite the 3-year treatment-free period. As a reminder, BRUKINSA demonstrated roughly one-third fewer grade 3, 4 infections versus ibrutinib in the ALPINE study. The VO arm also showed a 67% nominally increased risk of death versus ibrutinib. These findings are quite consistent with data from other recent studies, such as AMPLIFY, where the AVO regimen was not FDA-approved. In fact, the FDA specifically called out the higher death rate due to infections from the AVO arm. In our view, this profile stands in direct opposition to what patients want and deserve from a fixed-duration treatment.

John Oyler: First, after 1 year of VO, severe infections continued to climb for 3 years while the patient was off treatment, as seen in blue. These infections are serious, often requiring hospitalization and IV antibiotics. Second, even after 4 years, severe infections were still higher with VO than with continuous ibrutinib, despite the 3-year treatment-free period. As a reminder, BRUKINSA demonstrated roughly one-third fewer grade 3, 4 infections versus ibrutinib in the ALPINE study. The VO arm also showed a 67% nominally increased risk of death versus ibrutinib. These findings are quite consistent with data from other recent studies, such as AMPLIFY, where the AVO regimen was not FDA-approved. In fact, the FDA specifically called out the higher death rate due to infections from the AVO arm. In our view, this profile stands in direct opposition to what patients want and deserve from a fixed-duration treatment.

Speaker #2: These infections are serious, often requiring hospitalization and IV antibiotics. Second, even after four years, severe infections were still higher with VO than with continuous ibrutinib, despite the three-year treatment-free period.

Speaker #2: As a reminder, Brukinsa demonstrated roughly one-third fewer grade 3/4 infections versus ibrutinib in the ALPINE study. The VO arm also showed a 67% nominally increased risk of death versus ibrutinib.

Speaker #2: These findings are quite consistent with data from other recent studies, such as amplify, where the AVO regimen was not FDA approved. In fact, the FDA specifically called out the higher death rate due to infections from the AVO arm.

Speaker #2: In our view, this profile stands in direct opposition to what patients want and deserve from a fixed-duration treatment. And if you now look at the table on the right, for the highest-risk patients—roughly half of all CLL patients—VO shows notably lower PFS.

[Company Representative] (BeOne Medicines): If you now look at the table on the right, for the highest-risk patients, roughly half of all CLL patients, VO shows notably lower PFS. This data shows that patients have an approximately 50% higher chance of progressing within 6 years. 50%! Look, there's a narrative that the current fixed-duration options are good, and if someone I love was diagnosed with CLL, my first inclination might also be towards fixed duration. If I knew the disease had potentially 50% higher chance of progressing within 6 years, and if I knew that fixed duration wasn't reducing the risk of serious infection over 4 years, just accelerating it into the earlier years, I certainly would encourage them to think twice. The risk-benefit profile of current fixed-duration regimens simply does not justify a shift away from established continuous BTKI therapy.

John Oyler: If you now look at the table on the right, for the highest-risk patients, roughly half of all CLL patients, VO shows notably lower PFS. This data shows that patients have an approximately 50% higher chance of progressing within 6 years. 50%! Look, there's a narrative that the current fixed-duration options are good, and if someone I love was diagnosed with CLL, my first inclination might also be towards fixed duration. If I knew the disease had potentially 50% higher chance of progressing within 6 years, and if I knew that fixed duration wasn't reducing the risk of serious infection over 4 years, just accelerating it into the earlier years, I certainly would encourage them to think twice. The risk-benefit profile of current fixed-duration regimens simply does not justify a shift away from established continuous BTKI therapy.

Speaker #2: This data shows that patients have an approximately 50% higher chance of progressing within six years. 50%. Look, there's a narrative that the current fixed duration options are good.

Speaker #2: And if someone I love was diagnosed with CLL, my first inclination might also be towards fixed duration. But if I knew the disease had potentially 50% higher chance of progressing within six years, and if I knew that fixed duration wasn't reducing the risk of serious infection over four years, just accelerating it into the earlier years, I certainly would encourage them to think twice.

Speaker #2: The risk-benefit profile of current fixed-duration regimens simply does not justify a shift away from established continuous BTKi therapy. The evidence that existing time-limited therapies may not provide long-term outcomes comparable with Brukinza continues to build.

[Company Representative] (BeOne Medicines): The evidence that existing time-limited therapies may not provide long-term outcomes comparable with BRUKINSA continues to build. Here we can see three recently published match-adjusted indirect comparisons of BRUKINSA versus AV, VI, and VO, which reach that conclusion. These reflect the early trends we're seeing in real-world data. Our goal for patients that prefer a fixed-duration treatment option is simple. We aim to develop a more efficacious time-limited regimen that does not come with caveats or accommodations, and we believe ZS is that therapy. The clinical data being generated by combining the best-in-class BTK inhibitor with a potentially best-in-class BCL-2 inhibitor just looks different. With all the caveats of cross-trial comparison, ZS has demonstrated the highest undetectable MRD rate, the highest PFS for the respective follow-up when compared to other ven-based fixed-duration therapies. ZS shows a favorable safety profile with fewer high-grade adverse events and no deaths.

John Oyler: The evidence that existing time-limited therapies may not provide long-term outcomes comparable with BRUKINSA continues to build. Here we can see three recently published match-adjusted indirect comparisons of BRUKINSA versus AV, VI, and VO, which reach that conclusion. These reflect the early trends we're seeing in real-world data. Our goal for patients that prefer a fixed-duration treatment option is simple. We aim to develop a more efficacious time-limited regimen that does not come with caveats or accommodations, and we believe ZS is that therapy. The clinical data being generated by combining the best-in-class BTK inhibitor with a potentially best-in-class BCL-2 inhibitor just looks different. With all the caveats of cross-trial comparison, ZS has demonstrated the highest undetectable MRD rate, the highest PFS for the respective follow-up when compared to other ven-based fixed-duration therapies.

Speaker #2: Here we can see three recently published match-adjusted indirect comparisons of Brukinza versus AV, VI, and VO, which reached that conclusion. And these reflect the early trends we're seeing in real-world data.

Speaker #2: Our goal for patients that prefer a fixed duration treatment option is simple. We aim to develop a more efficacious, time-limited regimen that does not come with caveats or accommodations.

Speaker #2: And we believe ZS is that therapy. The clinical data being generated by combining the best-in-class BTK inhibitor with a potentially best-in-class BCL2 inhibitor just looks different.

Speaker #2: With all the caveats of cross-trial comparison, ZS is demonstrated the highest undetectable MRD rate the highest PFS for the respective follow-up when compared to other ven-based fixed duration therapies.

Speaker #2: ZS shows a favorable safety profile with fewer high-grade adverse events and no deaths. And in terms of patient convenience, we've not yet observed any clinical or laboratory TLS.

John Oyler: ZS shows a favorable safety profile with fewer high-grade adverse events and no deaths. In terms of patient convenience, we've not yet observed any clinical or laboratory TLS, and we're very optimistic that for most patients, only one clinic visit during ramp-up will be required after Xanu lead-in. The CLL landscape is roughly split evenly into patients who receive continuous BTK inhibitors and those who receive some form of fixed-duration treatment. Currently, BRUKINSA captures approximately half of the continuous BTK segment of the market. ZS will enable BeOne to participate in the other half of the market, where today we have no presence.

[Company Representative] (BeOne Medicines): In terms of patient convenience, we've not yet observed any clinical or laboratory TLS, and we're very optimistic that for most patients, only one clinic visit during ramp-up will be required after Xanu lead-in. The CLL landscape is roughly split evenly into patients who receive continuous BTK inhibitors and those who receive some form of fixed-duration treatment. Currently, BRUKINSA captures approximately half of the continuous BTK segment of the market. ZS will enable BeOne to participate in the other half of the market, where today we have no presence. In summary, BeOne remains the only company with fully owned, potentially best-in-class assets across three foundational MOAs in CLL, BRUKINSA, sonrotoclax, and our BTK CDAC. As I said earlier, we think it is time to start talking about a cure....

Speaker #2: And we're very optimistic that, for most patients, only one clinic visit during ramp-up will be required after Xanuvidin. Today, the CLL landscape is roughly split evenly into patients who receive continuous BTK inhibitors and those who receive some form of fixed-duration treatment.

Speaker #2: And currently, Brukinza captures approximately half of the continuous BTK segment of the market. ZS will enable B1 to participate in the other half of the market, where today we have no presence.

Speaker #2: In summary, B1 remains the only company with fully owned, potentially best-in-class assets across three foundational MOAs in CLL. Brukinza, Sonro, and our BTK CDAC.

John Oyler: In summary, BeOne remains the only company with fully owned, potentially best-in-class assets across three foundational MOAs in CLL, BRUKINSA, sonrotoclax, and our BTK CDAC. As I said earlier, we think it is time to start talking about a cure....All three of these foundational assets, whether as monotherapy or in combination, represent the next chapter in CLL innovation, raising the bar for patients everywhere. Now I'll pass it over to Aaron to provide the financial update.

Speaker #2: As I said earlier, we think it is time to start talking about a cure. All three of these foundational assets, whether as monotherapy or in combination, represent the next chapter in CLL innovation.

[Company Representative] (BeOne Medicines): All three of these foundational assets, whether as monotherapy or in combination, represent the next chapter in CLL innovation, raising the bar for patients everywhere. Now I'll pass it over to Aaron to provide the financial update.

Speaker #2: Raising the bar for patients everywhere. Now I'll pass it over to Aaron to provide the financial update. Thanks, John. I'm pleased to share our fourth quarter and full-year results as we delivered against all of the financial commitments that we established in the beginning of 2025.

Aaron: Thanks, John. I'm pleased to share our Q4 and full year results as we delivered against all of the financial commitments that we established in the beginning of 2025. Product revenue reached $1.5 billion in Q4, representing 32% year-over-year growth. BRUKINSA global revenues totaled $1.1 billion, growing 38% with strong performance across all geographies. For full year 2025, BRUKINSA global revenues were $3.9 billion, representing growth of 49%. As John shared earlier, BRUKINSA has established itself as the leading BTKI globally by an increasing margin as we close 2025. In the US, BRUKINSA Q4 sales were $845 million, driven by volume growth of approximately 30% versus Q4 2024.

Aaron Rosenberg: Thanks, John. I'm pleased to share our Q4 and full year results as we delivered against all of the financial commitments that we established in the beginning of 2025. Product revenue reached $1.5 billion in Q4, representing 32% year-over-year growth. BRUKINSA global revenues totaled $1.1 billion, growing 38% with strong performance across all geographies. For full year 2025, BRUKINSA global revenues were $3.9 billion, representing growth of 49%. As John shared earlier, BRUKINSA has established itself as the leading BTKI globally by an increasing margin as we close 2025. In the US, BRUKINSA Q4 sales were $845 million, driven by volume growth of approximately 30% versus Q4 2024.

Speaker #2: Product revenue reached $1.5 billion in the fourth quarter, representing 32% year-over-year growth. Brukinza global revenues totaled $1.1 billion, growing 38% with strong performance across all geographies.

Speaker #2: For full-year 2025, Brukinza global revenues were $3.9 billion, representing growth of 49%. And as John shared earlier, Brukinza has established itself as the leading BTKi globally by an increasing margin as we closed 2025.

Speaker #2: In the US, Brukinza fourth quarter sales were $845 million, driven by volume growth of approximately 30% versus Q4 2024. Our leadership is directly linked to the differentiated breadth, quality, and consistency of Brukinza's clinical data including those shared at ASH 2025.

Aaron: Our leadership is directly linked to the differentiated breadth, quality, and consistency of BRUKINSA's clinical data, including those shared at ASH 2025. Pricing dynamics in the United States were consistent with commentary provided last quarter, with a mid-single-digit pricing benefit on a year-over-year basis. These results include the previously mentioned typical seasonality benefits seen in the Q4 of the year for both current year performance and the 2024 baseline. Meanwhile, TEVIMBRA reported an 18% increase, reflecting continued market leadership in China. This growth was supplemented by contributions from launch markets. Our in-licensed products also showed continued strength, growing 9% year-over-year. We continue to observe solid execution across geographies. The US remains our largest market, generating $850 million with year-over-year growth of 38%.

Aaron Rosenberg: Our leadership is directly linked to the differentiated breadth, quality, and consistency of BRUKINSA's clinical data, including those shared at ASH 2025. Pricing dynamics in the United States were consistent with commentary provided last quarter, with a mid-single-digit pricing benefit on a year-over-year basis. These results include the previously mentioned typical seasonality benefits seen in the Q4 of the year for both current year performance and the 2024 baseline. Meanwhile, TEVIMBRA reported an 18% increase, reflecting continued market leadership in China. This growth was supplemented by contributions from launch markets. Our in-licensed products also showed continued strength, growing 9% year-over-year. We continue to observe solid execution across geographies. The US remains our largest market, generating $850 million with year-over-year growth of 38%.

Speaker #2: Pricing dynamics in the United States were consistent with commentary provided last quarter, with a mid-single-digit pricing benefit on a year-over-year basis. These results include the previously mentioned typical seasonality benefits seen in the fourth quarter of the year for both current-year performance and the 2024 baseline.

Speaker #2: Meanwhile, to Vimro reported an 18% increase, reflecting continued market leadership in China. This growth was supplemented by contributions from launch markets. Our in-license products also showed continued strength, growing 9% year-over-year.

Speaker #2: We continue to observe solid execution across geographies. The US remains our largest market, generating $850 million, with year-over-year growth of 38%. China revenue totaled $399 million, an 11% increase compared to the fourth quarter of 2024, supported by to Vimro and Brukinza's market leadership, and growth from our in-license assets.

Aaron: China revenue totaled $399 million, an 11% increase compared to Q4 2024, supported by TEVIMBRA and BRUKINSA's market leadership and growth from our in-licensed assets. Europe contributed $174 million, with 53% year-over-year growth as we continue our launch trajectory with BRUKINSA, with increased share across all major markets. Rest of world markets grew 74%, driven by market expansion and new launches. Now, turning to the other components of our GAAP P&L, my commentary will be on a full year basis, unless otherwise noted. Gross margin improved to 87% from approximately 84% in the prior year. This year-over-year improvement primarily reflects the benefits from favorable product mix, price, and product cost efficiencies.

Aaron Rosenberg: China revenue totaled $399 million, an 11% increase compared to Q4 2024, supported by TEVIMBRA and BRUKINSA's market leadership and growth from our in-licensed assets. Europe contributed $174 million, with 53% year-over-year growth as we continue our launch trajectory with BRUKINSA, with increased share across all major markets. Rest of world markets grew 74%, driven by market expansion and new launches. Now, turning to the other components of our GAAP P&L, my commentary will be on a full year basis, unless otherwise noted. Gross margin improved to 87% from approximately 84% in the prior year. This year-over-year improvement primarily reflects the benefits from favorable product mix, price, and product cost efficiencies.

Speaker #2: Europe contributed $174 million, with 53% year-over-year growth as we continue our launch trajectory with Brukinza with increased share across all major markets. And rest of world markets grew 74%, driven by market expansion and new launches.

Speaker #2: Now turning to the other components of our GAAP P&L and my commentary will be on a full-year basis unless otherwise noted. Gross margin improved to 87% from approximately 84% in the prior year.

Speaker #2: This year-over-year improvement primarily reflects the benefits from favorable product mix, price, and product cost efficiencies. Operating expenses grew by 12%, totaling $4.2 billion, as we are investing with discipline to support our commercial growth and rapidly advance our innovative pipeline.

Aaron: OpEx grew by 12%, totaling $4.2 billion, as we are investing with discipline to support our commercial growth and rapidly advance our innovative pipeline. Income from operations totaled $447 million, showcasing the inflection in 2025 to a company that is at scale and profitable. Bridging from operating to net income, other income and expense included a non-recurring $40 million equity investment impairment in Q4. Income tax expense totaled $130 million for 2025, increasing from $112 million in 2024, including $25 million of non-recurring tax expenses and $20 million of timing-related tax expenses in certain geographies. These effects, in part driven by our valuation allowance status, disproportionately impacted Q4.

Aaron Rosenberg: OpEx grew by 12%, totaling $4.2 billion, as we are investing with discipline to support our commercial growth and rapidly advance our innovative pipeline. Income from operations totaled $447 million, showcasing the inflection in 2025 to a company that is at scale and profitable. Bridging from operating to net income, other income and expense included a non-recurring $40 million equity investment impairment in Q4. Income tax expense totaled $130 million for 2025, increasing from $112 million in 2024, including $25 million of non-recurring tax expenses and $20 million of timing-related tax expenses in certain geographies. These effects, in part driven by our valuation allowance status, disproportionately impacted Q4.

Speaker #2: Income from operations totaled $447 million, showcasing the inflection in 2025 to accompany that is at scale and profitable. Bridging from operating to net income, other income and expense included a non-recurring $40 million equity investment impairment in the fourth quarter.

Speaker #2: Income tax expense totaled $130 million for 2025, increasing from $112 million in 2024, including $25 million of non-recurring tax expenses and $20 million of timing-related tax expenses in certain geographies.

Speaker #2: These effects in part driven by our valuation allowance status disproportionately impacted the fourth quarter. Altogether, and including these one-time items, net income reached $287 million in GAAP with GAAP diluted earnings per ADS of $2.53.

Aaron: Altogether, and including these one-time items, net income reached $287 million in GAAP, with GAAP diluted earnings per ADS of $2.53. Our non-GAAP P&L includes adjustments for typical items with a full reconciliation provided in the appendix. Non-GAAP income from operations totaled $1.1 billion in fiscal 2025, up from $45 million in 2024. Non-GAAP net income came in at $918 million for full year 2025, which translates to diluted non-GAAP earnings per ADS of $8.09. We continued our strong trend of cash flow generation with free cash flow of $380 million in Q4. Full year 2025, free cash flow was over $940 million. Now, turning to our 2026 financial guidance.

Aaron Rosenberg: Altogether, and including these one-time items, net income reached $287 million in GAAP, with GAAP diluted earnings per ADS of $2.53. Our non-GAAP P&L includes adjustments for typical items with a full reconciliation provided in the appendix. Non-GAAP income from operations totaled $1.1 billion in fiscal 2025, up from $45 million in 2024. Non-GAAP net income came in at $918 million for full year 2025, which translates to diluted non-GAAP earnings per ADS of $8.09. We continued our strong trend of cash flow generation with free cash flow of $380 million in Q4. Full year 2025, free cash flow was over $940 million. Now, turning to our 2026 financial guidance.

Speaker #2: Our non-GAAP P&L includes adjustments for typical items with a full reconciliation provided in the appendix. Non-GAAP income from operations totaled $1.1 billion in fiscal 2025, up from $45 million.

Speaker #2: In 2024, and non-GAAP net income came in at $918 million for full-year 2025, which translates to diluted non-GAAP earnings per ADS of $8.09. We continued our strong trend of cash flow generation, with free cash flow of $380 million in Q4.

Speaker #2: Full-year 2025 free cash flow was over $940 million. Now, turning to our 2026 financial guidance, we expect another strong year of revenue growth with continued global leadership for Brukinza.

Aaron: We expect another strong year of revenue growth with continued global leadership for BRUKINSA. We anticipate that the US will continue to see strong demand growth with relatively stable net pricing. Growth is anticipated in all markets and will benefit from continued global expansion in important rest-of-world markets. We anticipate modest initial contributions from our launches of Senradicdab and zanidatamab, as physicians begin to gain experience with these medicines ahead of launches in their respective larger market opportunities. We are pleased that these practice-changing medicines are becoming available to patients as they fulfill important unmet medical needs. In total, we project 2026 revenue to be between $6.2 billion to $6.4 billion.

Aaron Rosenberg: We expect another strong year of revenue growth with continued global leadership for BRUKINSA. We anticipate that the US will continue to see strong demand growth with relatively stable net pricing. Growth is anticipated in all markets and will benefit from continued global expansion in important rest-of-world markets. We anticipate modest initial contributions from our launches of Senradicdab and zanidatamab, as physicians begin to gain experience with these medicines ahead of launches in their respective larger market opportunities. We are pleased that these practice-changing medicines are becoming available to patients as they fulfill important unmet medical needs. In total, we project 2026 revenue to be between $6.2 billion to $6.4 billion.

Speaker #2: We anticipate that the US will continue to see strong demand growth, with relatively stable net pricing. Growth is anticipated in all markets and will benefit from continued global expansion in important rest-of-world markets.

Speaker #2: We anticipate modest initial contributions from our launches of Sunrata Clocks and Zana Databank as physicians begin to gain experience with these medicines ahead of launches in their respective larger market opportunities.

Speaker #2: We are pleased that these practice-changing medicines are becoming available to patients as they fulfill important unmet medical needs. In total, we project 2026 revenue to be between $6.2 billion to $6.4 billion.

Speaker #2: As you model quarterly phasing for 2026, please recall that we expect similar seasonality in shipping weeks in Q1 2026 as we observed in Q1 2025.

Aaron: As you model quarterly phasing for 2026, please recall that we expect similar seasonality and shipping weeks in Q1 2026, as we observed in Q1 2025, and therefore, we believe it is more useful to consider year-over-year growth rates in this upcoming period. Our GAAP gross margin percentage is expected to be in the high 80% range, with continued benefit from mix and a full year of productivity from improvements implemented last year. Operating expenses on a GAAP basis are anticipated to be between $4.7 and $4.9 billion. This level of investment ensures we are positioned to capture the full value of our commercial and late-stage pipeline opportunities. GAAP operating income is expected to be between $700 and $800 million, and non-GAAP operating income is expected to be between $1.4 and $1.5 billion.

Aaron Rosenberg: As you model quarterly phasing for 2026, please recall that we expect similar seasonality and shipping weeks in Q1 2026, as we observed in Q1 2025, and therefore, we believe it is more useful to consider year-over-year growth rates in this upcoming period. Our GAAP gross margin percentage is expected to be in the high 80% range, with continued benefit from mix and a full year of productivity from improvements implemented last year. Operating expenses on a GAAP basis are anticipated to be between $4.7 and $4.9 billion. This level of investment ensures we are positioned to capture the full value of our commercial and late-stage pipeline opportunities. GAAP operating income is expected to be between $700 and $800 million, and non-GAAP operating income is expected to be between $1.4 and $1.5 billion.

Speaker #2: And therefore, we believe it is more useful to consider year-over-year growth rates in this upcoming period. Our GAAP gross margin percentage is expected to be in the high 80% range, with continued benefit from mix and a full-year productivity from improvements implemented last year.

Speaker #2: Operating expenses on a GAAP basis are anticipated to be between $4.7 and $4.9 billion. This level of investment ensures we are positioned to capture the full value of our commercial and late-stage pipeline opportunities.

Speaker #2: GAAP operating income is expected to be between $700 and $800 million, and non-GAAP operating income is expected to be between $1.4 and $1.5 billion.

Speaker #2: In terms of other income and expenses, we expect expenses to be between $25 to $50 million, this includes interest expense associated with the royalty pharma arrangement.

Aaron: In terms of other income and expenses, we expect expenses to be between $25 to 50 million. This includes interest expense associated with the Royalty Pharma arrangement. Turning to income taxes, where we have historically been an evaluation allowance, whereby our accumulated deferred tax assets have a reserve against them. Given our recent history of earnings, we believe that there may be sufficient positive evidence to recognize a portion of these assets in 2026. The exact timing and magnitude are uncertain, but we believe that a potential reversal would result in a material tax benefit to the income tax provision when recognized. When this reversal occurs, we will reflect deferred taxes in our financial statements, and our effective tax rate will become a more meaningful and predictable metric. We will provide additional updates on income taxes throughout the year.

Aaron Rosenberg: In terms of other income and expenses, we expect expenses to be between $25 to 50 million. This includes interest expense associated with the Royalty Pharma arrangement. Turning to income taxes, where we have historically been an evaluation allowance, whereby our accumulated deferred tax assets have a reserve against them. Given our recent history of earnings, we believe that there may be sufficient positive evidence to recognize a portion of these assets in 2026. The exact timing and magnitude are uncertain, but we believe that a potential reversal would result in a material tax benefit to the income tax provision when recognized. When this reversal occurs, we will reflect deferred taxes in our financial statements, and our effective tax rate will become a more meaningful and predictable metric. We will provide additional updates on income taxes throughout the year.

Speaker #2: Turning to income taxes, where we have historically been in a valuation allowance—whereby our accumulated deferred tax assets have a reserve against them. Given our recent history of earnings, we believe that there may be sufficient positive evidence to recognize a portion of these assets in 2026.

Speaker #2: The exact timing and magnitude are uncertain, but we believe that a potential reversal would result in a material tax benefit to the income tax provision when recognized.

Speaker #2: When this reversal occurs, we will reflect deferred taxes in our financial statements, and our effective tax rate will become a more meaningful and predictable metric.

Speaker #2: We will provide additional updates on income taxes throughout the year. In summary, we are pleased with our performance in 2025, and like our setup for continued growth and financial strengthening as reflected in our 2026 guidance.

Aaron: In summary, we are pleased with our performance in 2025, like our setup for continued growth and financial strengthening as reflected in our 2026 guidance. I would be remiss if I did not take this opportunity to thank our global teams across all parts of BeOne for their incredible dedication to our company's purpose, the corresponding results that can be seen so clearly in our financial performance. With that, I'd like to pass the call over to Lai.

Aaron Rosenberg: In summary, we are pleased with our performance in 2025, like our setup for continued growth and financial strengthening as reflected in our 2026 guidance. I would be remiss if I did not take this opportunity to thank our global teams across all parts of BeOne for their incredible dedication to our company's purpose, the corresponding results that can be seen so clearly in our financial performance. With that, I'd like to pass the call over to Lai.

Speaker #2: I would be remiss if I did not take this opportunity to thank our global teams across all parts of B1 for their incredible dedication to our company's purpose, and the corresponding results that can be seen so clearly in our financial performance.

Speaker #2: And with that, I'd like to pass the call over to Lai.

Speaker #1: Thank you, Aaron. Hi, everyone. Thanks for joining us today. 2025 has been a standout year for B1 R&D. Most notably, it was a breakout year for Sono.

Wang Lai: Thank you, Aaron. Hi, everyone. Thanks for joining us today. 2025 has been a standout year for BeOne R&D. Most notably, it was a breakout year for Sono. We achieved our first global approvals in China for relapsed refractory MCL and the CLL. In addition, regulatory submissions for relapsed refractory MCL are under review in both the US and the EU, with FDA approval expected in the first half of this year. Our BTK degrader continues to advance steadily towards registration. In 2025, we initiated 3 Phase 3 studies, including a head-to-head trial versus Jaypirca. In solid tumors, we also made a strong progress. TEVIMBRA delivered a positive Phase 3 readout in HER2-positive gastric cancer in combination with zanidatamab and chemotherapy. Importantly, the next wave of innovation is here.

Lai Wang: Thank you, Aaron. Hi, everyone. Thanks for joining us today. 2025 has been a standout year for BeOne R&D. Most notably, it was a breakout year for Sono. We achieved our first global approvals in China for relapsed refractory MCL and the CLL. In addition, regulatory submissions for relapsed refractory MCL are under review in both the US and the EU, with FDA approval expected in the first half of this year. Our BTK degrader continues to advance steadily towards registration. In 2025, we initiated 3 Phase 3 studies, including a head-to-head trial versus Jaypirca. In solid tumors, we also made a strong progress. TEVIMBRA delivered a positive Phase 3 readout in HER2-positive gastric cancer in combination with zanidatamab and chemotherapy. Importantly, the next wave of innovation is here.

Speaker #1: We achieved our first global approvals in China for relaxed refractory MCL and CLL. In addition, regulatory submissions for relaxed refractory MCL are under review in both the US and the EU.

Speaker #1: With FDA approval, expected in the first half of this year. Our BDK degrader continues to advance steadily towards registration. In 2025, we initiated three phase three studies including a head-to-head trial versus Purdo.

Speaker #1: In solitumers, we also made a strong progress. December delivered a positive phase three readout in HER2 positive gastric cancer, in combination with Zana Datamab and chemotherapy.

Speaker #1: Importantly, the next wave of innovation is here. In 2025 alone, five assets achieved the clinical POC. And over the past two years, we have advanced 17 new molecular entities into the clinic.

Wang Lai: In 2025 alone, five assets achieved a clinical POC, and over the past two years, we have advanced 17 new molecule entities into the clinic. BeOne has moved us through two defining chapters in our history. In the first 10 years, we built it from the ground up. With limited capabilities, we delivered the two breakthrough medicines, BRUKINSA and TEVIMBRA, and a proof that BeOne could innovate at the highest level. The second chapter, over the past five years, was about skill and readiness. We invested heavily to build a powerful discovery engine and a truly differentiated global clinical development superhighway, transforming BeOne from a company with isolated wins into one capable of repeatable success. Today, we're positioned better than ever to deliver a continuous stream of innovation. 2026 marks the beginning of a new era for BeOne.

Lai Wang: In 2025 alone, five assets achieved a clinical POC, and over the past two years, we have advanced 17 new molecule entities into the clinic. BeOne has moved us through two defining chapters in our history. In the first 10 years, we built it from the ground up. With limited capabilities, we delivered the two breakthrough medicines, BRUKINSA and TEVIMBRA, and a proof that BeOne could innovate at the highest level. The second chapter, over the past five years, was about skill and readiness. We invested heavily to build a powerful discovery engine and a truly differentiated global clinical development superhighway, transforming BeOne from a company with isolated wins into one capable of repeatable success. Today, we're positioned better than ever to deliver a continuous stream of innovation. 2026 marks the beginning of a new era for BeOne.

Speaker #1: B1 has moved through two defining chapters in our history. In the first 10 years, we built from the ground up with limited capabilities we delivered two breakthrough medicines for cancer and Cavembera.

Speaker #1: And it proved that B1 could innovate at the highest level. The second chapter, over the past five years, was about scale and readiness. We invested heavily to build a powerful discovery engine and a truly differentiated global clinical development superhighway, transforming B1 from a company with isolated wins into one capable of repeatable success.

Speaker #1: Today, we're positioned better than ever to deliver a continuous stream of innovation. 2026 marks the beginning of a new era for B1. Over the next three years, we'll focus on four priorities.

Wang Lai: Over the next three years, we are focused on four parties. First, we'll deepen our leadership in CLL, building on our three foundational medicines. Second, we'll expand across hematological malignancies, including indolent and aggressive lymphomas, as well as AML. Third, we'll establish BeOne as an oncology powerhouse in solid tumors, with leadership in three strategically chosen subtypes, driven by both internal innovation and external partnerships. Finally, we plan to advance one to two potential cornerstone immunology assets towards registration. It took us 15 years to build our foundational CLL franchise. We believe we can move faster and do even better across other diseases. With greater skill and a sense of urgency, we can reach far more patients than ever before. In CLL, today, BRUKINSA is approved for both treatment-naive and the relapsed/refractory patients, giving us a strong foundation.

Lai Wang: Over the next three years, we are focused on four parties. First, we'll deepen our leadership in CLL, building on our three foundational medicines. Second, we'll expand across hematological malignancies, including indolent and aggressive lymphomas, as well as AML. Third, we'll establish BeOne as an oncology powerhouse in solid tumors, with leadership in three strategically chosen subtypes, driven by both internal innovation and external partnerships. Finally, we plan to advance one to two potential cornerstone immunology assets towards registration. It took us 15 years to build our foundational CLL franchise. We believe we can move faster and do even better across other diseases. With greater skill and a sense of urgency, we can reach far more patients than ever before. In CLL, today, BRUKINSA is approved for both treatment-naive and the relapsed/refractory patients, giving us a strong foundation.

Speaker #1: First, we'll deepen our leadership in CLL. Building on our three foundational medicines, second, we'll expand across hematological malignancies including indolent and aggressive lymphomas as well as AML.

Speaker #1: Third, we'll establish B1 as an oncology powerhouse in solitumers. With leadership in three strategically chosen subtypes, driven by both internal innovation and external partnerships.

Speaker #1: And finally, we plan to advance one to two potential cornerstone immunology assets towards registration. It took us 15 years to build our foundational CLL franchise.

Speaker #1: We believe we can move faster and do even better across other diseases. With greater scale and a sense of urgency, we can reach far more patients than ever before.

Speaker #1: In CLL, today Burkina is pooled for both treatment naive and relaxed refractory patients, giving us a strong foundation. Looking ahead, in the frontline setting, Burkina will serve as the foundational therapy either as continued use for patients who prefer finite therapy as a potentially best-in-class fixed duration regimen in combination with Sono.

Wang Lai: Looking ahead, in the front-line setting, BRUKINSA will serve as the foundational therapy, either as continued use for patients who prefer final therapy as a potentially best-in-class fixed-duration regimen in combination with Sono. In the relapsed/refractory setting, BeOne will offer BTK CDAC and other therapies. We see a potential accelerated approval opportunity for our BTK CDAC as a continued use monotherapy as early as next year. There are 3 phase 3 studies ongoing to establish strong evidence versus current standard cares. Beyond that, we believe the BTK CDAC and the Sono combination has the potential to deliver best-in-class fixed-duration therapy for relapsed/refractory patients with strong efficacy, safety, and convenience. A phase 3 study is being planned. Finally, we're also developing an alternative fixed-duration option, combining Sono with anti-CD20 therapies. Currently being tested head-to-head against venetoclax in a phase 3 study.

Lai Wang: Looking ahead, in the front-line setting, BRUKINSA will serve as the foundational therapy, either as continued use for patients who prefer final therapy as a potentially best-in-class fixed-duration regimen in combination with Sono. In the relapsed/refractory setting, BeOne will offer BTK CDAC and other therapies. We see a potential accelerated approval opportunity for our BTK CDAC as a continued use monotherapy as early as next year. There are 3 phase 3 studies ongoing to establish strong evidence versus current standard cares. Beyond that, we believe the BTK CDAC and the Sono combination has the potential to deliver best-in-class fixed-duration therapy for relapsed/refractory patients with strong efficacy, safety, and convenience. A phase 3 study is being planned. Finally, we're also developing an alternative fixed-duration option, combining Sono with anti-CD20 therapies. Currently being tested head-to-head against venetoclax in a phase 3 study.

Speaker #1: In the relaxed refractory setting, B1 will offer BDK-CDAC anchored therapies with a potential accelerated approval opportunity for our BDK-CDAC as a continued use monotherapy as early as next year.

Speaker #1: There are three phase three studies ongoing to establish strong evidence versus current standard cares. Beyond that, we believe the BDK-CDAC and the Sono combination has the potential to deliver best-in-class fixed duration therapy for relaxed refractory patients.

Speaker #1: With strong efficacy, safety, and convenience. A phase three study is being planned. Finally, we're also developing an alternative fixed duration option, combining Sono with anti-CD20 therapies.

Speaker #1: Currently being tested head-to-head against Venetoclax in a phase three study. We're also advancing our three foundational hematology assets across non-CLL indications. This molecules have demonstrated strong activity across multiple basal malignancies.

Wang Lai: We're also advancing our 3 foundational hematology assets across non-CLL indications. These molecules have demonstrated strong activity across multiple B-cell malignancies, including mantle cell lymphoma, Waldenström macroglobulinemia, follicular lymphoma, and marginal zone lymphoma. We're particularly excited about the Phase 3 interim analysis for Zanyu in combination with rituximab in treatment-naive mantle cell lymphoma, expected in the first half of this year. If successful, this would represent the first chemotherapy-free regimen in this setting. In addition, we're expanding Soro into multiple myeloma, with plans to initiate a pivotal Phase 3 study in combination with CD38 antibody and dexamethasone by the end of this year. 2026 will also be the year we expand beyond BTK and the BCL-2 MOAs in the hematology oncology. A new wave of assets is entering the clinic, led by our proprietary off-the-shelf iPSC-derived gamma delta T-cell, with tough genetic engineering modifications.

Lai Wang: We're also advancing our 3 foundational hematology assets across non-CLL indications. These molecules have demonstrated strong activity across multiple B-cell malignancies, including mantle cell lymphoma, Waldenström macroglobulinemia, follicular lymphoma, and marginal zone lymphoma. We're particularly excited about the Phase 3 interim analysis for Zanyu in combination with rituximab in treatment-naive mantle cell lymphoma, expected in the first half of this year. If successful, this would represent the first chemotherapy-free regimen in this setting. In addition, we're expanding Soro into multiple myeloma, with plans to initiate a pivotal Phase 3 study in combination with CD38 antibody and dexamethasone by the end of this year. 2026 will also be the year we expand beyond BTK and the BCL-2 MOAs in the hematology oncology. A new wave of assets is entering the clinic, led by our proprietary off-the-shelf iPSC-derived gamma delta T-cell, with tough genetic engineering modifications.

Speaker #1: Including mantle cell lymphoma, water-strong macroglobulinemia, follicle lymphoma, and marginal zone lymphoma. We're particularly excited about the phase three intramanalysis for Zanu in combination with Rituximab in treatment naive mantle cell lymphoma.

Speaker #1: Expected in the first half of this year. If successful, this would represent the first chemotherapy-free regimen in this setting. In addition, we're expanding Sono into multiple myeloma, with plans to initiate a pivotal phase three study in combination with CD30 antibody and dexamethasone by the end of this year.

Speaker #1: 2026, we'll also be the year we expand the Beyond BDK and the BCL2 MOAs in the hematology oncology. A new wave of assets is entering the clinic.

Speaker #1: Led by our proprietary off-the-shelf iPSC-derived gamma delta T cell therapy. With 12 genetic engineering modifications, this program is highly differentiated and designed to overcome many of the limitations of the existing off-shelf cell therapies.

Wang Lai: This program is highly differentiated and designed to overcome many of the limitations of the existing off-shelf cell therapies. I'm very excited about its potential in the clinic. In parallel, we're advancing T-cell engagers and T-cell boosters for B-cell malignancies, particularly for aggressive lymphomas, to address challenges such as kill managing loss and inadequate or unsustained T-cell activation. For AML and MDS, we're building a focused portfolio to address the significant unmet medical needs. Beyond the Soro, this includes a first-in-indication CASX inhibitor, supported by strong translational data, and a next-generation MENIN inhibitor designed to overcome all known resistance mutations. We also have additional undisclosed pre-clinical programs on the way that will continue to fuel our future pipeline. In summary, we have built a hematology portfolio defined by durability, differentiation, and depth, positioning BeOne for sustained impact well beyond our current leadership areas.

Lai Wang: This program is highly differentiated and designed to overcome many of the limitations of the existing off-shelf cell therapies. I'm very excited about its potential in the clinic. In parallel, we're advancing T-cell engagers and T-cell boosters for B-cell malignancies, particularly for aggressive lymphomas, to address challenges such as kill managing loss and inadequate or unsustained T-cell activation. For AML and MDS, we're building a focused portfolio to address the significant unmet medical needs. Beyond the Soro, this includes a first-in-indication CASX inhibitor, supported by strong translational data, and a next-generation MENIN inhibitor designed to overcome all known resistance mutations. We also have additional undisclosed pre-clinical programs on the way that will continue to fuel our future pipeline. In summary, we have built a hematology portfolio defined by durability, differentiation, and depth, positioning BeOne for sustained impact well beyond our current leadership areas.

Speaker #1: I'm very excited about its potential in the clinic. In parallel, we're advancing T cell engagers and T cell boosters for basal malignancies. Particularly, for aggressive lymphomas, to address challenges such as tumor managing loss, and inadequate or unsustained T cell activation.

Speaker #1: For ML and MDS, we're building a focused portfolio to address the significance of metamedical needs. Beyond the Sono, this includes a first-in-indication Cas6 inhibitor, supported by strong translational data, and a next-generation MANA inhibitor designed to overcome all known resistance mutations.

Speaker #1: We also have additional undisclosed preclinical programs on the way that we'll continue to fuel our future pipeline. In summary, we have built a hematology portfolio defined by durability, differentiation, and the depth, positioning B1 for sustained impact well beyond our current leadership areas.

Speaker #1: With that, let me turn to solitumers. Previously, our solitumer focus was largely on immuno-oncology. Over the last two years, we have fundamentally re-engineered the portfolio.

Wang Lai: With that, let me turn to solid tumors. Previously, our solid tumor focus was largely on immuno-oncology. Over the last 2 years, we have fundamentally reengineered the portfolio, shifting towards critical oncogenical signaling pathways across breast, gynecological, lung, and gastrointestinal cancers, using multiple therapeutic modalities. As you can see on the slide, we now have more than 20 assets across these focused disease areas. Among them, 5 programs have achieved the proof of concept in 2025. I will walk you through these key assets now. First, based on strong emerging efficacy and the safety data from phase I expansion cohorts, we plan to initiate a phase III trial in frontline hormone receptor-positive breast cancer in the first half of 2026. The safety profile suggests potentially best-in-class hematological safety with manageable gastrointestinal toxicity.

Lai Wang: With that, let me turn to solid tumors. Previously, our solid tumor focus was largely on immuno-oncology. Over the last 2 years, we have fundamentally reengineered the portfolio, shifting towards critical oncogenical signaling pathways across breast, gynecological, lung, and gastrointestinal cancers, using multiple therapeutic modalities. As you can see on the slide, we now have more than 20 assets across these focused disease areas. Among them, 5 programs have achieved the proof of concept in 2025. I will walk you through these key assets now. First, based on strong emerging efficacy and the safety data from phase I expansion cohorts, we plan to initiate a phase III trial in frontline hormone receptor-positive breast cancer in the first half of 2026. The safety profile suggests potentially best-in-class hematological safety with manageable gastrointestinal toxicity.

Speaker #1: Shifting towards critical oncogenical signaling pathways across breast gynecological, lung, and gastrointestinal cancers. Using multiple therapeutic modalities. As you can see on the slide, we now have more than 20 assets across this focused disease areas.

Speaker #1: Among them, five programs have achieved approved concept in 2025, and I will walk you through these key assets now. First, based on strong emerging efficacy, and the safety data from phase one expansion cohorts, we plan to initiate a phase three trial in frontline hormone receptor positive breast cancer in the first half of 2026.

Speaker #1: The safety profile suggests potentially best-in-class hematological safety with manageable gastrointestinal toxicity. The phase three study will compel BGB43395 against the physician's choice of CDK4/6 inhibitor in combination with letrozole, with progression-free survival by central radiology review as a primary endpoint.

Wang Lai: The Phase 3 study will compare BGB-43395 against the physician's choice of CDK4/6 inhibitor in combination with letrozole, with progression-free survival by central radiology review as the primary endpoint. Beyond the CDK4, we have four additional solid tumor programs advancing rapidly towards registration, all supported by compelling and evolving clinical data. B7-H4 ADC, encouraging activity in gynecological cancers and the triple-negative breast cancer. A Phase 3 study is expected to start within one year. GPC3x4-1BB bispecific. The strength of the positive data from this program has been a pleasant surprise, showing very exciting monotherapy signals in PD-1 pretreated HCC patients in its first in-human study. A pivotal trial will be initiated before year-end. Beyond defined inhibitor, this asset stands out with potentially best-in-class potency, selectivity, and brain penetration.

Lai Wang: The Phase 3 study will compare BGB-43395 against the physician's choice of CDK4/6 inhibitor in combination with letrozole, with progression-free survival by central radiology review as the primary endpoint. Beyond the CDK4, we have four additional solid tumor programs advancing rapidly towards registration, all supported by compelling and evolving clinical data. B7-H4 ADC, encouraging activity in gynecological cancers and the triple-negative breast cancer. A Phase 3 study is expected to start within one year. GPC3x4-1BB bispecific. The strength of the positive data from this program has been a pleasant surprise, showing very exciting monotherapy signals in PD-1 pretreated HCC patients in its first in-human study. A pivotal trial will be initiated before year-end. Beyond defined inhibitor, this asset stands out with potentially best-in-class potency, selectivity, and brain penetration.

Speaker #1: Beyond the CDK4, we have four additional solitumer programs advancing rapidly towards registration. All supported by compelling and evolving clinical data. B7H4ADC encourages activity in gynecological cancers and the triple-negative breast cancer.

Speaker #1: A phase three study is expected to start within one year. GPC341BB bispecific. The strength of the positive data from this program has been a pleasant surprise.

Speaker #1: Showing very exciting monotherapy signals in PD-1 pre-treated HCC patients in its first-in-treatment study. A pivotal trial will be initiated before year-end. Beyond defined inhibitor, this asset stands out with potentially best-in-class potency, selectivity, and brain data. We're accelerating this program into frontline non-small cell lung cancer.

Wang Lai: Based on emerging Phase I data, we're accelerating this program into frontline non-small cell lung cancer. CDAC, we're seeing promising monotherapy activity in heavily pretreated patients and are planning for the pivotal trials. It is important to note that all four assets have been in the clinic for less than two years, and the three for less than 18 months. This is a level of focus, efficiency, and execution we aim to deliver across the portfolio. Together, these five POC assets represent a step change in BeOne solid tumor impacts. With multiple modalities, rapid clinical execution, and a clear path to registration, we're no longer building a pipeline. We're building a solid tumor franchise, and this is only the beginning. To complement our growing portfolio, we have also invested heavily in clinical execution capability.

Lai Wang: Based on emerging Phase I data, we're accelerating this program into frontline non-small cell lung cancer. CDAC, we're seeing promising monotherapy activity in heavily pretreated patients and are planning for the pivotal trials. It is important to note that all four assets have been in the clinic for less than two years, and the three for less than 18 months. This is a level of focus, efficiency, and execution we aim to deliver across the portfolio. Together, these five POC assets represent a step change in BeOne solid tumor impacts. With multiple modalities, rapid clinical execution, and a clear path to registration, we're no longer building a pipeline. We're building a solid tumor franchise, and this is only the beginning. To complement our growing portfolio, we have also invested heavily in clinical execution capability.

Speaker #1: CADC, we're seeing promising monotherapy activity in heavily pre-treated patients and are planning for the pivotal trials. It is important to note that all four assets have been the clinic for less than two years.

Speaker #1: And the three for less than 18 months. This is the level of focus, efficiency, and execution we aim to deliver across the portfolio. Together, these five POC assets represent a step change in B1 Solitumer impact.

Speaker #1: With multiple modalities, rapid clinical execution, and a clear path to registration, we're no longer building a pipeline. We're building a solitumer franchise. And this is only the beginning.

Speaker #1: To complement our growing portfolio, we have also invested heavily in clinical execution capability. We now call this our global clinical development superhighway. Designed to deliver industry-leading speed, quality, and reliability.

Wang Lai: We now call this our global clinical development superhighway, designed to deliver industry-leading speed, quality, and reliability. Let me give you a few examples. Over the past 2 years, we have completed around 200 dose escalation cohorts across multiple first-in-human studies, with a median of just 1.5 months per cohort. The industry norm is roughly 3 months. In late-stage development, last year, we completed enrollment of a CELESTIAL-TNCLL study with around 700 CLL patients across 20 countries and more than 200 sites in just 14 months. As you know, CLL is not an easy indication to enroll. On the regulatory side, our most recent NDA filing, sonrotoclax's initial filing with the FDA in mantle cell lymphoma, was completed within 1 month of top-line data. Industry standards are typically 4 to 6 months. Finally, we're equipping these super highways with AI and automation.

Lai Wang: We now call this our global clinical development superhighway, designed to deliver industry-leading speed, quality, and reliability. Let me give you a few examples. Over the past 2 years, we have completed around 200 dose escalation cohorts across multiple first-in-human studies, with a median of just 1.5 months per cohort. The industry norm is roughly 3 months. In late-stage development, last year, we completed enrollment of a CELESTIAL-TNCLL study with around 700 CLL patients across 20 countries and more than 200 sites in just 14 months. As you know, CLL is not an easy indication to enroll. On the regulatory side, our most recent NDA filing, sonrotoclax's initial filing with the FDA in mantle cell lymphoma, was completed within 1 month of top-line data. Industry standards are typically 4 to 6 months. Finally, we're equipping these super highways with AI and automation.

Speaker #1: Let me give you a few examples. Over the past two years, we have completed around 200 dose escalation cohorts across multiple first-in-treatment studies. With a median of just 1.5 months per cohort.

Speaker #1: The industry norm is roughly three months. In late-stage development, last year, we completed enrollment of a Celestial TNCOL study with around 700 COL patients across 20 countries and more than 200 sites in just 14 months.

Speaker #1: And as you know, COL is not an easy indication to enroll. On the regulatory side, our most recent NDA filing, Sonos initial filing with the FDA in mantle cell lymphoma, was completed within one month of top-line data.

Speaker #1: Industrial standard are typically four to six months. Finally, we're equipping this superhighway with AI and automation today, we can already deliver near real-time data analysis and insights across all early-stage clinical trials.

Wang Lai: Today, we can already deliver near real-time data analysis and insights across all early-stage clinical trials. Over the next two to three years, we expect the AI and automation to unlock even greater gains in speed, quality, and decision-making. This global clinical superhighway is a core competitive advantage for BeOne. We look forward to sharing continued progress in future updates. Very quickly, on 2026 catalysts, I have touched on most of them already. Let me highlight a few key ones I haven't mentioned yet. First, we just initiated a global Phase 3 study of ZS versus AV in treatment IV CLL, directly comparing two all-oral fixed duration regimens. Second, in the first half of this year, we expect to file tislelizumab for HER2-positive gastric cancer in combination with standard docetaxel and TMZ.

Lai Wang: Today, we can already deliver near real-time data analysis and insights across all early-stage clinical trials. Over the next two to three years, we expect the AI and automation to unlock even greater gains in speed, quality, and decision-making. This global clinical superhighway is a core competitive advantage for BeOne. We look forward to sharing continued progress in future updates. Very quickly, on 2026 catalysts, I have touched on most of them already. Let me highlight a few key ones I haven't mentioned yet.

Speaker #1: Over the next two to three years, we expect the AI and automation to unlock even greater gains in speed, quality, and decision-making. This global clinical superhighway is a core competitive advantage for B1.

Speaker #1: We look forward to sharing continued progress in future updates. Very quickly, on 2026 catalysts, I have touched on most of them already, so let me highlight a few key ones I haven't mentioned yet.

Speaker #1: First, we just initiated a global phase three study of ZS versus AV in treatment IV COL directly comparing two all-oral fixed duration regimens. Second, in the first half of this year, we expect to file catalytism map for HER2 positive gastric cancer in combination with standard DAT map and chemo.

Lai Wang: First, we just initiated a global Phase 3 study of ZS versus AV in treatment IV CLL, directly comparing two all-oral fixed duration regimens. Second, in the first half of this year, we expect to file tislelizumab for HER2-positive gastric cancer in combination with standard docetaxel and TMZ. Finally, in immunology, we anticipate multiple proof-of-concept readouts this year, including BTK CDAC in CSU and IRAK4 CDAC in OA. I will now turn it back to John.

Speaker #1: And finally, in immunology, we anticipate multiple proof of concept readouts this year. Including BTKCDAC in CSU and IRAC4CDAC in RA. I will now turn it back to John.

Wang Lai: Finally, in immunology, we anticipate multiple proof-of-concept readouts this year, including BTK CDAC in CSU and IRAK4 CDAC in OA. I will now turn it back to John.

Speaker #2: Thank you so much, Lai, for the comments. Really appreciate it. I think with that, we're going to jump to Q&A and operator please limit the number of questions to ensure we have time to hear from as many attendees as possible, but please go ahead.

[Company Representative] (BeOne Medicines): Thank you so much, Lai, for the comments. Really appreciate it. I think with that, we're gonna jump to Q&A. Operator, you know, please limit the number of questions to ensure we have time to hear from as many attendees as possible, but please go ahead.

John Oyler: Thank you so much, Lai, for the comments. Really appreciate it. I think with that, we're gonna jump to Q&A. Operator, you know, please limit the number of questions to ensure we have time to hear from as many attendees as possible, but please go ahead.

Speaker #3: Thank you. 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.

Operator: Thank you. 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 Michael Schmidt at Guggenheim Partners. Please unmute your line and ask your question.

Operator: Thank you. 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 Michael Schmidt at Guggenheim Partners. Please unmute your line and ask your question.

Speaker #3: 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 Michael Schmidt at Guggenheim Partners.

Speaker #3: Please unmute your line and ask your question.

Speaker #4: Hey, guys. Good morning and thanks for picking up questions. I had a commercial question around the BTK inhibitor market and Prokinca. Specifically, could you comment some more on how you think about potential net pricing development in the BTK inhibitor market longer term, especially as we see your competitor products enter the CMS drug price negotiation program this year and next?

Michael Schmidt: Hey, guys. Good morning, and thanks for taking our questions. I had a commercial question around the BTK inhibitor market and BRUKINSA. Specifically, could you comment some more on how you think about potential net pricing development in the BTK inhibitor market longer term, especially as we see your competitor products enter the CMS drug price negotiation program this year and next? Thanks so much.

Michael Schmidt: Hey, guys. Good morning, and thanks for taking our questions. I had a commercial question around the BTK inhibitor market and BRUKINSA. Specifically, could you comment some more on how you think about potential net pricing development in the BTK inhibitor market longer term, especially as we see your competitor products enter the CMS drug price negotiation program this year and next? Thanks so much.

Speaker #4: Thanks so much.

Speaker #2: Yes. Yeah, thank you. Nice to hear from you. I think from the perspective in this space, as we've tried to lay out, this is a very differentiated value proposition with Prokinca.

[Company Representative] (BeOne Medicines): Yeah. Yeah, thank you. Nice to hear from you. I think from the perspective in this space, as we've tried to lay out, this is a very differentiated value proposition with BRUKINSA versus any of the current therapies that are on the market. You know, whether it's safety profile or whether it's just the long-term PFS and overall survival, this is, you know, in our mind, a best-in-class product that has demonstrated the translation of its mechanism of action into real clinical results. I think at this point, you know, certainly there are challenges for those other products, but, you know, we're just standing by the value that the products are creating for patients and it's there. That's why we're showing it to you. Could we jump to the next question, please?

John Oyler: Yeah. Yeah, thank you. Nice to hear from you. I think from the perspective in this space, as we've tried to lay out, this is a very differentiated value proposition with BRUKINSA versus any of the current therapies that are on the market. You know, whether it's safety profile or whether it's just the long-term PFS and overall survival, this is, you know, in our mind, a best-in-class product that has demonstrated the translation of its mechanism of action into real clinical results. I think at this point, you know, certainly there are challenges for those other products, but, you know, we're just standing by the value that the products are creating for patients and it's there. That's why we're showing it to you. Could we jump to the next question, please?

Speaker #2: Versus any of the current therapies that are on the market. Whether it's safety profile or whether it's just the long-term PFS and overall survival, this is in our mind a best-in-class product that has demonstrated the translation of its mechanism of action into real clinical results.

Speaker #2: And I think at this point, certainly there are challenges for those other products. But we're just standing by the value that they products are creating for patients.

Speaker #2: And it's there. That's why we're showing it to you. So could we jump to the next question, please?

Speaker #3: Yes, of course. Our next question comes from Yaron Werber with Cohen. Please unmute your line and ask your question.

Operator: Yes, of course. Our next question comes from Yaron Werber with Cohen. Please unmute your line and ask your questions.

Operator: Yes, of course. Our next question comes from Yaron Werber with Cohen. Please unmute your line and ask your questions.

Speaker #5: Great. Thanks so much and congrats on really a lot of progress. I've a question I think a lot of us have been getting. In the guidance, what do you assume in terms of competition from AV or a GPRCO is probably sort of late, late in the year?

Yaron Werber: Great, thanks so much and congrats on really a lot of progress. I have a question I think a lot of us have been getting. In the guidance, what are you assuming in terms of competition from AV or Jaypirca, because it's probably sort of late in the year? Maybe secondly, in terms of SONRO for MCL, both in China and in the US, can you just help us think through a little bit, you know, kind of what's the initial opportunity? Thank you.

Yaron Werber: Great, thanks so much and congrats on really a lot of progress. I have a question I think a lot of us have been getting. In the guidance, what are you assuming in terms of competition from AV or Jaypirca, because it's probably sort of late in the year? Maybe secondly, in terms of SONRO for MCL, both in China and in the US, can you just help us think through a little bit, you know, kind of what's the initial opportunity? Thank you.

Speaker #5: And then maybe secondly, in terms of Sonoro for MCL, both in China and in the US, can you just help us think through a little bit kind of what's the initial opportunity?

Speaker #5: Thank you.

Speaker #2: So Matt, perhaps you can answer that a little bit and then we can jump to Xiaobin.

[Company Representative] (BeOne Medicines): Matt, perhaps you can answer that a little bit, and then we can jump to Xiaobin.

John Oyler: Matt, perhaps you can answer that a little bit, and then we can jump to Xiaobin.

Speaker #6: Sure. Yeah, I can provide some perspective. On Amplify and then JPRCO as well, as you know, AVO was not approved and as we've discussed before, AV, while approved, was studied only in a very young and very fit patient population.

Matt Shaulis: Sure, yeah. I can provide some perspective on AMPLIFY and then Jaypirca as well. As you know, AVO was not approved, and as we've discussed before, AV, while approved, was studied only in a very young and very fit patient population, which had a median age of around 61. We think those are some natural limitations there. Moreover, I think that we continue to be very confident in the clinical profile of BRUKINSA. You know, we've outlined, as you heard from John, the importance of meeting some criteria for treatment in CLL, deep and durable remissions, PFS, safety, and convenience. We see that AV doesn't live up to that standard. Certainly on MRD and PFS, it's very straightforward, with safety and tolerability. I think that situation holds true.

Matt Shaulis: Sure, yeah. I can provide some perspective on AMPLIFY and then Jaypirca as well. As you know, AVO was not approved, and as we've discussed before, AV, while approved, was studied only in a very young and very fit patient population, which had a median age of around 61. We think those are some natural limitations there. Moreover, I think that we continue to be very confident in the clinical profile of BRUKINSA. You know, we've outlined, as you heard from John, the importance of meeting some criteria for treatment in CLL, deep and durable remissions, PFS, safety, and convenience. We see that AV doesn't live up to that standard. Certainly on MRD and PFS, it's very straightforward, with safety and tolerability. I think that situation holds true.

Speaker #6: Which had a median age of around 61. So we think those are some natural limitations there. Moreover, I think that we continue to be very confident in the clinical profile of Prokinca.

Speaker #6: We've outlined, as you heard from John, the importance of meeting some criteria for treatment in CLL, deep and durable remissions, PFS safety, and convenience.

Speaker #6: And we see that AV doesn't live up to that standard. Certainly on MRD and PFS, it's very straightforward. With safety and tolerability, I think that situation holds true.

Speaker #6: And then the convenience is still tied to some of the cumbersome nature of venue utilization. Now, as for JPRCO, we have seen some data back at ASH and overall that body of evidence doesn't yield the level of compelling data that we think is going to really change a treatment paradigm in the earlier lines of therapy.

Xiaobin Wu: ... and then the convenience is still tied to some of the cumbersome nature of venue utilization. As for Jakafi, we have seen some data back at ASH, and overall, that body of evidence doesn't yield the level of compelling data that we think is gonna really change the treatment paradigm in the earlier lines of therapy. Particularly, we continue to hear from clinicians that that evidence does not rise to the level of burning a line of therapy with a continuous BTK, and that they will continue to position Jakafi after the continuous BTKs. Obviously, in our case, that bodes really well for BRUKINSA.

Matt Shaulis: ... and then the convenience is still tied to some of the cumbersome nature of venue utilization. As for Jakafi, we have seen some data back at ASH, and overall, that body of evidence doesn't yield the level of compelling data that we think is gonna really change the treatment paradigm in the earlier lines of therapy. Particularly, we continue to hear from clinicians that that evidence does not rise to the level of burning a line of therapy with a continuous BTK, and that they will continue to position Jakafi after the continuous BTKs. Obviously, in our case, that bodes really well for BRUKINSA.

Speaker #6: Particularly, we continue to hear from clinicians that that evidence does not rise to the level of burning a line of therapy with a continuous BTK.

Speaker #6: And that they will continue to position JPRCO after the continuous BTKs, and obviously in our case, that bodes really well for Prokinca.

Speaker #5: So Chana, Soron, approved beginning of this year, 2026. And we launched so quickly after that approval. And since launch, this is about six weeks.

Wang Lai: China, sonrotoclax approved, beginning of this year, 2026, and we launched so quickly after that approval. Since launch, this is about 6 weeks, and the reaction in the market has been very positive. We medicated or doctor prescribed for over 300 patients, and the approved indication is relapsed, refractory mantle cell lymphoma and CLL. So far, the safety profile has been also very good. No major safety concern observed. That's a very positive experience from all the major China hematology centers. It looks like it's very positive, and we are aiming definitely to be a market leader for the BCL2 market going forward. This is to approve the BCL2 in China.

Xiaobin Wu: China, sonrotoclax approved, beginning of this year, 2026, and we launched so quickly after that approval. Since launch, this is about 6 weeks, and the reaction in the market has been very positive. We medicated or doctor prescribed for over 300 patients, and the approved indication is relapsed, refractory mantle cell lymphoma and CLL. So far, the safety profile has been also very good. No major safety concern observed. That's a very positive experience from all the major China hematology centers. It looks like it's very positive, and we are aiming definitely to be a market leader for the BCL2 market going forward. This is to approve the BCL2 in China. One is, the venetoclax, and another one is, China local, lisaftoclax. Yeah.

Speaker #5: And the reaction in the market has been very positive with medicated or doctor-prescribed for over 300 patients. And the approved indication is relapsed refractory mental state lymphoma and CLL.

Speaker #5: And so far, the safety profile has been also very good. So no major safety concern observed. So there's a very positive experience from all the major China hematology centers.

Speaker #5: It looks like it's very positive and we are aiming definitely to be market leader for the BCL2 market going forward. This is to approve the BCL2 in China one is the venatoclax and another one is China local Liza.

Wang Lai: One is, the venetoclax, and another one is, China local, lisaftoclax. Yeah.

Speaker #5: Yeah.

[Company Representative] (BeOne Medicines): Great. Thanks so much, Xiaoming. Can we jump to the next question, please?

John Oyler: Great. Thanks so much, Xiaoming. Can we jump to the next question, please?

Speaker #2: Great. Thanks so much, Xiaobin. Can we jump to the next question, please?

Speaker #3: Our next question comes from Zi Chen with Goldman Sachs. Please unmute your line and ask your question.

Operator: Our next question comes from Ziyi Chen with Goldman Sachs. Please unmute your line and ask your question.

Operator: Our next question comes from Ziyi Chen with Goldman Sachs. Please unmute your line and ask your question.

Ziyi Chen: Thank you so much, congrats on the results. I got one question on the immunology pipeline you mentioned about. I think this is probably the first time during the earnings briefing, you mentioned about immunology is gonna be the next thing, you know, out of the four pillars you are gonna be working on. Lai mentioned about there are gonna be one or two cornerstone therapies that you could potentially pursue in moving into pivotal studies for immunology. Could you elaborate a little bit more about what's gonna be the strategy for the immunology beyond hematology and solid tumor, that you are already being very strong at? What's gonna be over the next few years, what's gonna be the path and a journey towards becoming some meaningful player in immunology?

Speaker #5: Thank you so much and congrats on the results. I got one question on the immunology pipeline you mentioned about. I think this is probably the first time during the earnings briefing you mentioned about immunology going to be the next thing.

Ziyi Chen: Thank you so much, congrats on the results. I got one question on the immunology pipeline you mentioned about. I think this is probably the first time during the earnings briefing, you mentioned about immunology is gonna be the next thing, you know, out of the four pillars you are gonna be working on. Lai mentioned about there are gonna be one or two cornerstone therapies that you could potentially pursue in moving into pivotal studies for immunology. Could you elaborate a little bit more about what's gonna be the strategy for the immunology beyond hematology and solid tumor, that you are already being very strong at? What's gonna be over the next few years, what's gonna be the path and a journey towards becoming some meaningful player in immunology?

Speaker #5: Out of the four pillars, you're going to be working on. So Lai mentioned about there are going to be one or two cornerstone therapies.

Speaker #5: That you could potentially pursue and move into pivotal studies for immunology. Could you elaborate a little bit more about what's going to be the strategy for the immunology beyond hematology and solid tumor that B1 already being very strong at?

Speaker #5: And what's going to be over the next few years? What's going to be the paths and a journey towards becoming some meaningful player in immunology?

Speaker #2: Great. Please, Lai. Thanks for the question.

[Company Representative] (BeOne Medicines): Great. Please, please, Lai, thanks for the question.

John Oyler: Great. Please, please, Lai, thanks for the question.

Wang Lai: Yeah, thanks for the question. In our preclinical pipeline, we have roughly about 20% of our assets are focused on immunology. We acknowledge we're still a young player in the immunology space. For us, we're gonna be optimistic, looking for potential opportunity to be the first in class or best in class. Our goal is in the next about 2 to 3 years, to identify 1 or 2 molecules which we feel like can be a cornerstone asset for us to build around. We're looking forward to share with you the updates in the upcoming additional, you know, the earning calls. There are some very exciting molecules we're really developing at this moment. Some of that is already in the clinical stage.

Lai Wang: Yeah, thanks for the question. In our preclinical pipeline, we have roughly about 20% of our assets are focused on immunology. We acknowledge we're still a young player in the immunology space. For us, we're gonna be optimistic, looking for potential opportunity to be the first in class or best in class. Our goal is in the next about 2 to 3 years, to identify 1 or 2 molecules which we feel like can be a cornerstone asset for us to build around. We're looking forward to share with you the updates in the upcoming additional, you know, the earning calls. There are some very exciting molecules we're really developing at this moment. Some of that is already in the clinical stage.

Speaker #4: Yeah. Thanks for the question. In our preclinical pipeline, we have roughly about 20% of our assets are focused on immunology. We acknowledge we're still a young player.

Speaker #4: In the immunology space, for us, we're going to be optimistic looking for potential opportunity to be the first in class or best in class.

Speaker #4: Our goal is in the next about two to three years to identify one or two molecules which we feel like can be a cornerstone asset for us to build around.

Speaker #4: So we're looking forward to share with you the updates in the upcoming additional earning calls. But there are some very exciting molecules we're really developing at this moment.

Speaker #4: Some of that is already in the clinical stage.

Speaker #2: Thanks so much. Can we have another question, please?

[Company Representative] (BeOne Medicines): Thanks so much. Can we have another question, please?

John Oyler: Thanks so much. Can we have another question, please?

Speaker #3: Yes. The next question comes from Nigal Notomovits from Citi. Please unmute your line and ask your question.

Operator: Yes. The next question comes from Yigal Nochomovitz from Citi. Please unmute your line and ask your question.

Operator: Yes. The next question comes from Yigal Nochomovitz from Citi. Please unmute your line and ask your question.

Yigal Nochomovitz: Hi. Great, can you hear me?

Yigal Nochomovitz: Hi. Great, can you hear me?

Speaker #4: Hi. Great. Can you hear me? I just wanted to hi, John. You made some excellent arguments regarding the fixed duration and the inferior options today.

[Company Representative] (BeOne Medicines): Yeah.

John Oyler: Yeah.

Yigal Nochomovitz: Hi, John. You know, you made some excellent arguments regarding the fixed duration and the inferior options today versus a continuous BTK. I just wonder if you could just clarify, you know, if ZS does become the fixed duration regimen of choice and the standard of care in treatment naive, could you just clarify, you know, how you're not gonna sacrifice the long-duration revenues with continuous BRUKINSA? I think that would be helpful to understand a bit better, please. Thank you.

Yigal Nochomovitz: Hi, John. You know, you made some excellent arguments regarding the fixed duration and the inferior options today versus a continuous BTK. I just wonder if you could just clarify, you know, if ZS does become the fixed duration regimen of choice and the standard of care in treatment naive, could you just clarify, you know, how you're not gonna sacrifice the long-duration revenues with continuous BRUKINSA? I think that would be helpful to understand a bit better, please. Thank you.

Speaker #4: Versus a continuous BTK. But I just wonder if you could just clarify. With ZS does become the fixed duration regimen of choice and the standard of care in treatment naive.

Speaker #4: Could you just clarify how you're not going to sacrifice the long duration revenues with continuous Prokinca. I think that would be helpful to understand a bit better, please.

Speaker #4: Thank you.

Speaker #2: Sure. Sure. As Aaron's going to dig into that.

[Company Representative] (BeOne Medicines): Sure. Sure, Aaron's gonna.

John Oyler: Sure. Sure, Aaron's gonna.

Xiaobin Wu: Thanks-

Aaron Rosenberg: Thanks-

[Company Representative] (BeOne Medicines): Jump into that.

John Oyler: Jump into that.

Xiaobin Wu: Thanks for the question, Nigel. You've seen the, you know, the different forms of the pie chart that John shared in his slides. You know, in the current dynamics, and that's a view on the US, the dynamics aren't too dissimilar outside the US, although fixed dose treatment for BCL-2 combinations are a bit more mature in Europe. You know, about half the market is receiving fixed-dose treatment, half's receiving continuous use, and as you saw in that view, you know, we're currently getting about 50% on a new patient basis for BRUKINSA. You know, what we're trying to state really clearly there is the combination of Zanrow plus zanubrutinib opens up 50% of the market where we don't play at all today.

Aaron Rosenberg: Thanks for the question, Nigel. You've seen the, you know, the different forms of the pie chart that John shared in his slides. You know, in the current dynamics, and that's a view on the US, the dynamics aren't too dissimilar outside the US, although fixed dose treatment for BCL-2 combinations are a bit more mature in Europe. You know, about half the market is receiving fixed-dose treatment, half's receiving continuous use, and as you saw in that view, you know, we're currently getting about 50% on a new patient basis for BRUKINSA.

Speaker #4: Thanks for the question, Nigal. And you've seen that a different forms of the pie chart that John shared in his slides. In the current dynamics, that's a view on the US, the dynamics aren't too dissimilar outside the US.

Speaker #4: Although fixed-dose treatment for BTK/BCL2 combinations is a bit more mature in Europe, about half the market is receiving fixed-dose treatment and half is receiving continuous use.

Speaker #4: And as you saw in that view, we're currently getting about 50% on the new patient basis for Prokinca. So what we're trying to say really clearly there is the combination of Sonro plus Zanubrutinib opens up 50% of the market where we don't play at all today.

Aaron Rosenberg: You know, what we're trying to state really clearly there is the combination of Zanrow plus zanubrutinib opens up 50% of the market where we don't play at all today. From that dimension, and as we continue to mature candidly in our market share within the continuous use class alone with BRUKINSA, we view this as very market expanding.

Speaker #4: So from that dimension and as we continue to mature candidly in our market share within the continuous use class alone with Prokinca, we view this as very market expanding.

Xiaobin Wu: From that dimension, and as we continue to mature candidly in our market share within the continuous use class alone with BRUKINSA, we view this as very market expanding.

Speaker #4: Thanks.

Yigal Nochomovitz: Thanks.

Yigal Nochomovitz: Thanks.

Speaker #2: Yeah. I think the promise is there and we're hopeful that the data translates as positively as we've seen so far. It really could fulfill the promise and the story that's being told now about fixed duration.

[Company Representative] (BeOne Medicines): Yeah, I think the promise is there, and we're hopeful that the data translates as positively as we've seen so far. You know, it really, you know, could fulfill the promise. You know, the story that's being told now about, you know, fixed duration. You know, were that to happen, that would be a really wonderful thing, but it would place us in a truly unique position. I think regardless of that, for this 50% of the population that is already on fixed duration, if we're anywhere near the data we're showing at this moment, it's just on every one of those boxes, you know, checking what would be required to be a best-in-class medicine. We're really, really excited about this opportunity.

John Oyler: Yeah, I think the promise is there, and we're hopeful that the data translates as positively as we've seen so far. You know, it really, you know, could fulfill the promise. You know, the story that's being told now about, you know, fixed duration. You know, were that to happen, that would be a really wonderful thing, but it would place us in a truly unique position. I think regardless of that, for this 50% of the population that is already on fixed duration, if we're anywhere near the data we're showing at this moment, it's just on every one of those boxes, you know, checking what would be required to be a best-in-class medicine. We're really, really excited about this opportunity. We just need to wait a little bit for a little more data to mature from that perspective.

Speaker #2: And were that to happen, that would be a really wonderful thing. But it would place us in a truly, truly unique position. I think regardless of that, for this 50% of the population, that is already on fixed duration, if we're anywhere near the data we're showing at this moment, it's just on every one of those boxes.

Speaker #2: Checking what would be required to be a best-in-class medicine. So we're really, really excited about this opportunity. We just need to wait a little bit for a little more data to mature.

[Company Representative] (BeOne Medicines): We just need to wait a little bit for a little more data to mature from that perspective.

Speaker #2: From that perspective.

Speaker #4: Thank you.

[Company Representative] (BeOne Medicines): Thank you.

Yigal Nochomovitz: Thank you.

Speaker #3: Thank you. Our next question comes from Renny Benjamin at Citizens GMP. Please unmute your line and ask your question.

Operator: Thank you. Our next question comes from Reni Benjamin at Citizens JMP. Please unmute your line and ask your question.

Operator: Thank you. Our next question comes from Reni Benjamin at Citizens JMP. Please unmute your line and ask your question.

Speaker #5: Hey, good morning, guys. Thanks for taking the questions and congratulations on a great year and the guidance that's provided. I guess my question is regarding the BTK degrader.

Reni Benjamin: Hey, good morning, guys. Thanks for taking the questions, and congratulations on a great year and the guidance that's provided. I guess that my question is regarding the BTK degrader. You had some, you know, pretty encouraging data that was presented at ASH. I thought that there was a potential for an accelerated approval in the first half of this year. I think it's been pushed out to the second half. Can you just kind of confirm that I'm reading that right, and can you provide some color as to what's causing the pushout and how we should be thinking about the first approval? Thank you.

Reni Benjamin: Hey, good morning, guys. Thanks for taking the questions, and congratulations on a great year and the guidance that's provided. I guess that my question is regarding the BTK degrader. You had some, you know, pretty encouraging data that was presented at ASH. I thought that there was a potential for an accelerated approval in the first half of this year. I think it's been pushed out to the second half. Can you just kind of confirm that I'm reading that right, and can you provide some color as to what's causing the pushout and how we should be thinking about the first approval? Thank you.

Speaker #5: You had some pretty encouraging data that was presented at Ash. I thought that there was the potential for an accelerated approval in the first half of this year.

Speaker #5: I think it's been pushed out to the second half. Can you just kind of confirm that I'm reading that right and can you provide some caller as to what's causing the push out and how we should be thinking about the first approval?

Speaker #5: Thank you.

Speaker #2: Great question. Amit, will you please respond?

[Company Representative] (BeOne Medicines): Great question. Amit, will you please respond?

John Oyler: Great question. Amit, will you please respond?

Speaker #6: Yeah, thank you for the question, Renny. So, I don't think there's been a change in terms of the timing and kind of how we're thinking about this.

Amit Agarwal: Yeah. Thank you for the question, Reni. I don't think there's been a change in terms of, you know, the timing and kind of how we're thinking about this. Obviously, this is a single-arm approach. In terms of what we're looking at there, is based on a single-arm trial. We're following that data and look forward to having the interactions with the FDA midyear and file based on our interactions with the FDA. There's really no change in terms of the timing there.

Amit Agarwal: Yeah. Thank you for the question, Reni. I don't think there's been a change in terms of, you know, the timing and kind of how we're thinking about this. Obviously, this is a single-arm approach. In terms of what we're looking at there, is based on a single-arm trial. We're following that data and look forward to having the interactions with the FDA midyear and file based on our interactions with the FDA. There's really no change in terms of the timing there.

Speaker #6: Obviously, this is a single-arm approach. And so in terms of what we're looking at there, is based on a single-arm trial. And so we're following that data and look forward to having the interactions with the FDA mid-year and file based on our interactions with the FDA.

Speaker #6: So there's really no change in terms of the timing there.

Speaker #5: Got it. Thank you.

Reni Benjamin: Got it. Thank you.

Reni Benjamin: Got it. Thank you.

Speaker #2: Next question, please.

[Company Representative] (BeOne Medicines): Next question, please.

John Oyler: Next question, please.

Speaker #3: Our next question comes from Sean Lahman at Morgan Stanley. Please unmute your line and ask your question.

Operator: Our next question comes from Sean Laaman at Morgan Stanley. Please unmute your line and ask your question. Sean, can you please unmute your line and ask your question?

Operator: Our next question comes from Sean Laaman at Morgan Stanley. Please unmute your line and ask your question. Sean, can you please unmute your line and ask your question?

Speaker #5: What's going on?

Speaker #3: Sean, can you please unmute your line and ask your question?

Speaker #7: Good morning, John and team. Sorry about that. And thank you for taking my question. Just trying to understand a bit better the long runway of growth potential for Prokinca.

Sean Laaman: Good morning, John and team. Sorry about that, thank you for taking my question. Just trying to understand a bit better, you know, the long runway of growth potential for BRUKINSA here. You did $3.9 billion at, I think for the year, at around 40% growth. CALQUENCE did, I think they did double-digit growth at, to get to $3.5 billion, and IMBRUVICA is growing negative mid-teens, but still did $2 billion. That's about, you know, $3.5 billion, where BRUKINSA is not operating, if you like, and clearly winning the battle against IMBRUVICA. Given the compelling data that you have to show best in class, what's the tipping point or what's the wrestle here to really start eating into that CALQUENCE share?

Sean Laaman: Good morning, John and team. Sorry about that, thank you for taking my question. Just trying to understand a bit better, you know, the long runway of growth potential for BRUKINSA here. You did $3.9 billion at, I think for the year, at around 40% growth. CALQUENCE did, I think they did double-digit growth at, to get to $3.5 billion, and IMBRUVICA is growing negative mid-teens, but still did $2 billion. That's about, you know, $3.5 billion, where BRUKINSA is not operating, if you like, and clearly winning the battle against IMBRUVICA. Given the compelling data that you have to show best in class, what's the tipping point or what's the wrestle here to really start eating into that CALQUENCE share?

Speaker #7: Here, you did 3.9 billion at, I think, for the year at around 40% growth. Calquence did, I think they did double-digit growth at to get to 3.5 billion.

Speaker #7: And Imbruvica is growing negative mid-teens, but still did 2 billion. So that's about 3.5 billion where Prokincer is not operating, if you like. And clearly, winning the battle against Imbruvica, but given the compelling data that you have to show best in class, what's the tipping point or what's the ressel here to really start eating into that Calquence share?

[Company Representative] (BeOne Medicines): Aaron, would you like to answer that?

Speaker #2: Aaron, would you like to answer that?

John Oyler: Aaron, would you like to answer that?

Speaker #4: No. Thanks, Sean. talking, we certainly feel very confident in the totality of the evidence for Prokinca. And ultimately, the dynamics you're describing in terms of our performance in the marketplace, it's the data that's resonating and ultimately translating to the growth that you've described.

Xiaobin Wu: Thanks. Thanks, Sean. You know, as we've been talking, you know, we certainly feel very confident in the totality of the evidence for BRUKINSA. Ultimately, the dynamics you're describing in terms of our performance in the marketplace, you know, it's the data that's resonating and ultimately translating to the growth that you've described. You know, as you look at our, the market share slide that we showed in the deck, you know, on a new patient share, we're currently getting about 50% of the continuous-use BTK market. We are the global market leader, but we're not quite at 50% yet because we continue to mature into that profile.

Aaron Rosenberg: Thanks. Thanks, Sean. You know, as we've been talking, you know, we certainly feel very confident in the totality of the evidence for BRUKINSA. Ultimately, the dynamics you're describing in terms of our performance in the marketplace, you know, it's the data that's resonating and ultimately translating to the growth that you've described. You know, as you look at our, the market share slide that we showed in the deck, you know, on a new patient share, we're currently getting about 50% of the continuous-use BTK market.

Speaker #4: As you look at the market share slide that we showed in the deck, on a new patient share, we're currently getting about 50% of the continuous use BTK market.

Speaker #4: We are the global market leader, but we're not quite at 50% yet because we continue to mature into that profile. So as you think about the growth for our business, is the continue maturation into our growth profile?

Aaron Rosenberg: We are the global market leader, but we're not quite at 50% yet because we continue to mature into that profile.s you think about the growth for our business, it's a continued maturation into our growth profile, and certainly, we believe, having the best-in-class medicine in the continuous use BTK space, there's more than ample opportunity to continue to grow share over time.

Xiaobin Wu: as you think about the growth for our business, it's a continued maturation into our growth profile, and certainly, we believe, having the best-in-class medicine in the continuous use BTK space, there's more than ample opportunity to continue to grow share over time.

Speaker #4: And certainly, we believe having the best-in-class medicine in the continuous use BTK space, there's more than ample opportunity to continue to grow share over time.

Speaker #2: Yeah. And I think our challenge is really just get people to look at the data. It speaks for itself. That is a portion of the data that we're sharing on this call, whether it's the long-term data, whether it's the head-to-head data, whether it's the combination data versus their combination data.

[Company Representative] (BeOne Medicines): Yeah. I think our challenge is really just get people to look at the data. It speaks for itself. You know, that is a portion of the data that we're sharing on this call, whether it's the long-term data, whether it's the head-to-head data, whether it's, you know, combination data versus their combination data. You know, every place you look, the story is the same. You know, there's, you know, work being done in real-world data from that perspective, too, but I just think it's this overwhelming body of evidence. You know, that's the challenge, you know. Of course, you know, we're the only person that wants to share that information. The rest of the industry, it may not be in their best interest, but it's really, really important that we share it for patients so that they're getting the best medicine.

John Oyler: Yeah. I think our challenge is really just get people to look at the data. It speaks for itself. You know, that is a portion of the data that we're sharing on this call, whether it's the long-term data, whether it's the head-to-head data, whether it's, you know, combination data versus their combination data. You know, every place you look, the story is the same. You know, there's, you know, work being done in real-world data from that perspective, too, but I just think it's this overwhelming body of evidence. You know, that's the challenge, you know. Of course, you know, we're the only person that wants to share that information. The rest of the industry, it may not be in their best interest, but it's really, really important that we share it for patients so that they're getting the best medicine.

Speaker #2: Every place you look, the story is the same. And there's work being done in real-world data from that perspective too. But I just think it's this overwhelming body of evidence.

Speaker #2: Any of that's the challenge. Of course, we're the only person that wants to share that information. The rest of the industry, it may not be in their best interest.

Speaker #2: But it's really, really important that we share it for patients so that they're getting the best medicine.

Speaker #7: Thank you.

Sean Laaman: Thank you.

Sean Laaman: Thank you.

Speaker #2: Can we jump to a new question?

[Company Representative] (BeOne Medicines): Can we jump to a new question?

John Oyler: Can we jump to a new question?

Speaker #3: Our next question comes from Chen Chen with UBS. Please unmute your line and ask your question.

Operator: Our next question comes from Chen Chen with UBS. Please unmute your line and ask your question.

Operator: Our next question comes from Chen Chen with UBS. Please unmute your line and ask your question.

Speaker #8: Thank you for taking my question. So my question is on B7H4 ADC. And actually, I think this is not in the model or in the valuation.

Chen Chen: Thank you for taking my question. My question is on B7-H4 ADC, and actually, I think this is not in the model or in the valuation right now, but I heard that you are going to initiate phase three, like, within the next 12 months. May I know that the clinical trial would be initiated in the first half or the second half?

Chen Chen: Thank you for taking my question. My question is on B7-H4 ADC, and actually, I think this is not in the model or in the valuation right now, but I heard that you are going to initiate phase three, like, within the next 12 months. May I know that the clinical trial would be initiated in the first half or the second half? It has showed some promising efficacy and safety in gynecology and some breast cancers. May we know, like, in which indication are you going to initiate this trial? Also, I think, the B7-H4 ADC is roughly like at least 12 months, like, later than our, like, tiers, B7-H4 ADC. What are the differentiation of this molecule? Thanks.

Speaker #8: Right now, but I heard that you are going to initiate phase three, like within the next 12 months. So may I know that in so the clinical trial would be initiated in the first half or the second half?

Speaker #8: And also, it has showed some promising efficacy and safety in gynecology and some breast cancers. So may we know in which indication are you going to initiate phase three trial?

Rebecca Liang: It has showed some promising efficacy and safety in gynecology and some breast cancers. May we know, like, in which indication are you going to initiate this trial? Also, I think, the B7-H4 ADC is roughly like at least 12 months, like, later than our, like, tiers, B7-H4 ADC. What are the differentiation of this molecule? Thanks.

Speaker #8: And also, I think the B7H4 ADC is roughly like at least like 12 months, like later than our peers' B7H4 ADC. So what are the differentiation of this molecule?

Speaker #8: Thanks.

Speaker #2: Thanks for the question, Mark. Could you address that, please?

[Company Representative] (BeOne Medicines): Thanks for the question. Mark, could you address that, please?

John Oyler: Thanks for the question. Mark, could you address that, please?

Speaker #5: Thank you very much for the question. So we're really pleased with the progress that's been made with our B7H4 targeting ADC. This has progressed swiftly through phase one dose escalation.

[Company Representative] (BeOne Medicines): Thank you very much for the question. We're really pleased with the progress that's been made with our B7-H4 targeting ADC. This has progressed swiftly through phase one dose escalation, and as you heard from Lai, we are planning to disclose efficacy and safety data for the dose escalation in the first half of the year at a major medical congress. We recognize that the competitive landscape, that there are a number of competing molecules, both within B7-H4 and more broadly within the Topoisomerase I conjugated ADC space, particularly in breast and gynecologic malignancies, which is why we're moving with urgency. I think that we will be able to speak in more detail regarding the differentiation of our compound once we disclose the data.

Mark Lanasa: Thank you very much for the question. We're really pleased with the progress that's been made with our B7-H4 targeting ADC. This has progressed swiftly through phase one dose escalation, and as you heard from Lai, we are planning to disclose efficacy and safety data for the dose escalation in the first half of the year at a major medical congress. We recognize that the competitive landscape, that there are a number of competing molecules, both within B7-H4 and more broadly within the Topoisomerase I conjugated ADC space, particularly in breast and gynecologic malignancies, which is why we're moving with urgency. I think that we will be able to speak in more detail regarding the differentiation of our compound once we disclose the data.

Speaker #5: And as you heard from Lai, we are planning to disclose efficacy and safety data for the dose escalation in the first half of the year at a major medical congress.

Speaker #5: We recognize that the competitive landscape that there are a number of competing molecules both within B7H4 and more broadly within the TOPO1 conjugated ADC space, particularly in breast and gynecologic malignancies, which is why we're moving with urgency I think that I, we will be able to speak in more detail regarding the differentiation of our compound once we disclose the data.

[Company Representative] (BeOne Medicines): Suffice to say, we're very happy with the emerging efficacy data and think that we also have a nice safety profile with no target-mediated toxicities beyond what one would expect for a Topoisomerase I conjugated ADC, and a good hematologic safety profile. It's checking all the boxes to be on a path for a phase three study start as soon as possible. Again, we'll be able to share more details about first indication for phase three versus subsequent indications for phase three as we disclose data throughout the year.

Speaker #5: But suffice to say, we're very happy with the emerging efficacy data and think that we also have a nice safety profile with no target-mediated toxicities beyond what one would expect for a TOPO1 conjugated ADC.

Mark Lanasa: Suffice to say, we're very happy with the emerging efficacy data and think that we also have a nice safety profile with no target-mediated toxicities beyond what one would expect for a Topoisomerase I conjugated ADC, and a good hematologic safety profile. It's checking all the boxes to be on a path for a phase three study start as soon as possible. Again, we'll be able to share more details about first indication for phase three versus subsequent indications for phase three as we disclose data throughout the year.

Speaker #5: And a good hematologic safety profile. So it's checking all the boxes to be on a path for a phase three study start as soon as possible.

Speaker #5: And again, we'll be able to share more details about first indication for phase three versus subsequent indications for phase three as we disclose data throughout the year.

[Company Representative] (BeOne Medicines): thanks, Mark. could we take two more questions, please?

Speaker #2: Thanks, Mark. And could we take two more questions, please?

John Oyler: thanks, Mark. could we take two more questions, please?

Speaker #3: Yes. Our next question comes from Leonard Timichev with RBC Capital Markets. Please unmute your line and ask your question.

Operator: Yes. Our next question comes from Leonid Timashev, with RBC Capital Markets. Please unmute your line and ask your question.

Operator: Yes. Our next question comes from Leonid Timashev, with RBC Capital Markets. Please unmute your line and ask your question.

Speaker #9: Hi, guys. Thanks for taking my question. I wanted to ask on the BTK degrader development pathway specifically on the phase threes. I guess given you're going to have a potential accelerator approval and you're running three phase three studies, I guess what's the incremental value of each of those studies?

Leonid Timashev: Hi, guys. Thanks for taking my question. I wanted to ask on the BTK degrader development pathway, specifically on the phase IIIs. I guess, even you're gonna have a potential accelerated approval, and you're running three phase III studies, I guess, what's the incremental value of each of those studies? I guess you need ultimately all three to fully realize the opportunity, or do you think you're still gonna have rapid uptake, you know, as the data starts to flow in over time? Thanks.

Leonid Timashev: Hi, guys. Thanks for taking my question. I wanted to ask on the BTK degrader development pathway, specifically on the phase IIIs. I guess, even you're gonna have a potential accelerated approval, and you're running three phase III studies, I guess, what's the incremental value of each of those studies? I guess you need ultimately all three to fully realize the opportunity, or do you think you're still gonna have rapid uptake, you know, as the data starts to flow in over time? Thanks.

Speaker #9: I guess do you need ultimately all three to fully realize the opportunity, or do you think you're still going to have wrap-it-up take as the data starts to flow?

Speaker #9: In over time. Thanks.

Speaker #2: Thank you. Amit, would you like to answer that question?

[Company Representative] (BeOne Medicines): Thank you. Amit, would you like to answer that question?

John Oyler: Thank you. Amit, would you like to answer that question?

Speaker #10: Yeah. Thank you for that question. I think from a BTK degrader perspective, again, we're very encouraged by the data that we've seen so far.

Amit Agarwal: Yeah, thank you for that question. I think, you know, from a BTK degrader perspective, again, we're very encouraged by the data that we've seen so far. We do think that this is going to really be a foundational treatment as a BTK asset for the future. In terms of the phase 3, I think we're answering important questions with the phase 3 studies that we have right now, particularly with the two global phase 3 studies. I think, you know, one is in a slightly later line with the investigator's choice as a control arm. The other study is really a head-to-head study against bortezomib.

Amit Agarwal: Yeah, thank you for that question. I think, you know, from a BTK degrader perspective, again, we're very encouraged by the data that we've seen so far. We do think that this is going to really be a foundational treatment as a BTK asset for the future. In terms of the phase 3, I think we're answering important questions with the phase 3 studies that we have right now, particularly with the two global phase 3 studies. I think, you know, one is in a slightly later line with the investigator's choice as a control arm. The other study is really a head-to-head study against bortezomib.

Speaker #10: We do think that this is going to really be a foundational treatment as a BTK asset for the future. And in terms of the phase three, I think we're answering important questions with the phase three studies that we have right now, particularly with the two global phase three studies.

Speaker #10: I think one is in a slightly later line with the investigator's choice as a control arm, and then the other study is really a head-to-head study against vertebrate NIB.

Speaker #10: And so we do see incremental value, especially from that vertebrate NIB study, to be able to show that as far as that population is concerned, BTK degrader has a really sort of clear role in terms of the monotherapy.

Amit Agarwal: We do see incremental value, especially from that bortezomib study, to be able to show that as far as that population is concerned, the BTK degrader has a really sort of clear role in terms of the monotherapy. Beyond that, we are obviously, as Lai showed, working on a BTK degrader plus sonro combination as well. You'll continue to see us generate more data there.

Amit Agarwal: We do see incremental value, especially from that bortezomib study, to be able to show that as far as that population is concerned, the BTK degrader has a really sort of clear role in terms of the monotherapy. Beyond that, we are obviously, as Lai showed, working on a BTK degrader plus sonro combination as well. You'll continue to see us generate more data there.

Speaker #10: And then beyond that, we're obviously as Lai showed, working on a BTK degrader plus Sonro combination as well. And so you'll continue to see us generate more data there.

Speaker #2: Thanks, Amit. And are there any more questions or should we wrap up now?

[Company Representative] (BeOne Medicines): Thanks, Amit. Are there any more questions, or, should we wrap up now?

John Oyler: Thanks, Amit. Are there any more questions, or, should we wrap up now?

Speaker #3: We have one more question from Rebecca Liang from Bernstein. Please unmute your line and ask your question.

Operator: We have one more question from Rebecca Liang from Bernstein. Please unmute your line and ask your question.

Operator: We have one more question from Rebecca Liang from Bernstein. Please unmute your line and ask your question.

Speaker #11: Hi. Questions on the great results. And thank you for taking my question. So you showed a very interesting chart on the patient share between fixed duration and continuous therapies.

Rebecca Liang: Hi, congratulations on the great results, and thank you for taking my question. You showed a very interesting chart on the patient share between fixed duration and continuous therapies. I'm wondering how you see the future development between BRUKINSA and sonrotoclax after sonrotoclax plus BRUKINSA becomes a viable option. Given that now, the fixed duration therapy has half the patient share, but obviously much lower commercial sales. venetoclax, for example, only selling around $2 to 3 billion versus the whole BTK market at around $10 billion because of the limitation of fixed duration in treatment duration. How do you see the future commercial sales split between the two products? Even if there's maybe no immediate guidance for the long-term peak sales, but qualitatively, the split between the two products. Thank you.

Rebecca Liang: Hi, congratulations on the great results, and thank you for taking my question. You showed a very interesting chart on the patient share between fixed duration and continuous therapies. I'm wondering how you see the future development between BRUKINSA and sonrotoclax after sonrotoclax plus BRUKINSA becomes a viable option. Given that now, the fixed duration therapy has half the patient share, but obviously much lower commercial sales. venetoclax, for example, only selling around $2 to 3 billion versus the whole BTK market at around $10 billion because of the limitation of fixed duration in treatment duration. How do you see the future commercial sales split between the two products? Even if there's maybe no immediate guidance for the long-term peak sales, but qualitatively, the split between the two products. Thank you.

Speaker #11: I'm wondering how you see the future development between Burkinza and Sonro after Sonro plus Burkinza becomes a viable option. Given that now the fixed duration therapy has halved the patient share, but obviously, much lower commercial sales.

Speaker #11: So venetoclax, for example, only selling around 2 to 3 billion. Versus the whole BTK market at around 10 billion. Because of the limitation of fixed duration in treatment duration.

Speaker #11: So, how do you see the future commercial sales split between the two products? Even if there's maybe no immediate guidance for the long-term peak sales, but qualitatively, the split between the two products.

Speaker #11: Thank you.

[Company Representative] (BeOne Medicines): First of all, I would clarify that although, you know, half the patients in CLL, in that pie chart are listed as fixed duration, they're not all getting that. There's all sorts of other things, even chemo, surprisingly, that is still being given to patients. You know, first of all, as we move into that segment of the class, I think ven has been very limited by its usability, especially in the community setting. You know, I think that having a fixed duration treatment that can replace, you know, I don't know, I'd say some of these less evidence-based fixed duration treatments in that that are being used broadly in the community center, I think, is a huge value to patients.

John Oyler: First of all, I would clarify that although, you know, half the patients in CLL, in that pie chart are listed as fixed duration, they're not all getting that. There's all sorts of other things, even chemo, surprisingly, that is still being given to patients. You know, first of all, as we move into that segment of the class, I think ven has been very limited by its usability, especially in the community setting. You know, I think that having a fixed duration treatment that can replace, you know, I don't know, I'd say some of these less evidence-based fixed duration treatments in that that are being used broadly in the community center, I think, is a huge value to patients.

Speaker #2: First of all, I would clarify that although half the patients in CLL in that pie chart are listed as fixed duration, they're not all getting that.

Speaker #2: There's all sorts of other things. Even chemo surprisingly that is still being given to patients. So first of all, as we move into that segment of the class, I think then has been very limited by its usability, especially in the community setting.

Speaker #2: So I think that having a fixed duration treatment that can replace I don't know. I'd say some of these less evidence-based fixed duration treatments in that half that are being used broadly in the community center, I think is a huge, huge value to patients.

Speaker #2: And we would expect with the quality of the early data from that that this really could be a unique product combination within that 50% of the market for sure.

[Company Representative] (BeOne Medicines): you know, we would expect with the quality of the early data from that this really could be a unique product combination within that 50% of the market for sure. To be clear, there's lots of patients that have different prognosis in CLL. If we jump back to that, you have deletion 17p in unmutated patients. You also have mutated patients. About half of them are high-risk factored patients, and those patients are hard to handle for sure, and they're very hard for the current fixed-duration therapies to address. I don't have the slide number. Maybe someone will flash it to me. you know, when you go back to the slide that showed on the left-hand side, the infection rates associated with VO, on the right-hand side, you could look at the numbers there.

John Oyler: you know, we would expect with the quality of the early data from that this really could be a unique product combination within that 50% of the market for sure. To be clear, there's lots of patients that have different prognosis in CLL. If we jump back to that, you have deletion 17p in unmutated patients. You also have mutated patients. About half of them are high-risk factored patients, and those patients are hard to handle for sure, and they're very hard for the current fixed-duration therapies to address. I don't have the slide number. Maybe someone will flash it to me. you know, when you go back to the slide that showed on the left-hand side, the infection rates associated with VO, on the right-hand side, you could look at the numbers there.

Speaker #2: To be clear, there's lots of patients that have different prognosis in CLL. And if we jump back to that, you have deletion 17P and unmutated patients.

Speaker #2: You also have mutated patients. About half of them are high-risk factor patients. And those patients are hard to handle. For sure. And they're very hard for the current fixed duration therapies to address.

Speaker #2: I don't have the slide number. Maybe someone will flash it to me. But when you go back to the slide that showed on the left-hand side, the infection rates associated with VO on the right-hand side, you could look at the numbers there when you look at unmutated patients at deletion 17P patients.

[Company Representative] (BeOne Medicines): When you look at unmutated patients and deletion 17p patients, really, the outcomes are not good at all, and that's 'cause this is a harder disease to fight. Our hope is, you know, it would be great if, you know, our SZ doublet, which is all oral and easy to use and seems pretty safe, can treat all patients indefinitely, and that's truly a cure. You know, we don't have long-term follow-up yet on that. I think the early data makes it appear this is going to be better than any fixed-duration, you know, evidence-based therapy that you've seen to date. You know, we need time for that all to mature. Although it could be possible that this therapy, even in the highest-risk patients, is very compelling and can, you know, be as efficacious as continuous use for BRUKINSA, it's a high bar.

John Oyler: When you look at unmutated patients and deletion 17p patients, really, the outcomes are not good at all, and that's 'cause this is a harder disease to fight. Our hope is, you know, it would be great if, you know, our SZ doublet, which is all oral and easy to use and seems pretty safe, can treat all patients indefinitely, and that's truly a cure. You know, we don't have long-term follow-up yet on that. I think the early data makes it appear this is going to be better than any fixed-duration, you know, evidence-based therapy that you've seen to date. You know, we need time for that all to mature. Although it could be possible that this therapy, even in the highest-risk patients, is very compelling and can, you know, be as efficacious as continuous use for BRUKINSA, it's a high bar.

Speaker #2: Really, the outcomes are not good at all. And that's because this is a harder disease to fight. And our hope is it would be great if our SZ doublet, which is all oral and easy to use and seems pretty safe, can treat all patients, indefinitely, and that's truly, truly a cure.

Speaker #2: But we don't have long-term follow-up yet on that. I think the early data makes it appear this is going to be better than any fixed duration evidence-based therapy that you've seen to date.

Speaker #2: But we need time for that all to mature. And although it could be possible, that this therapy even in the highest risk patients is very compelling and can be as efficacious as continuous use Burkinza.

Speaker #2: It's a high bar. It's a really high bar. And we just go back and look on that scatter plot where VO is. On the scatter plot versus continuous ibrutinib, which is the comparison that's made in CLL17.

[Company Representative] (BeOne Medicines): It's a really high bar. You know, you just go back and look on that scatter plot where VO is on the scatter plot versus, you know, continuous ibrutinib, which is the comparison that's made in CLL17. Well, that's not the relevant comparison. The relevant comparison is continuous BRUKINSA, which, of course, has much, you know, better-looking 6-year data, you know, from a patient and physician perspective. You know, we need to see how the thing evolves, but it will take time. It'll take more than 6 years to understand and establish for those high-risk patients, is this really something that's as good as and competitive with, you know, long-term continuous BRUKINSA? It'd be great if it is, but, you know, nobody can be sure of that.

John Oyler: It's a really high bar. You know, you just go back and look on that scatter plot where VO is on the scatter plot versus, you know, continuous ibrutinib, which is the comparison that's made in CLL17. Well, that's not the relevant comparison. The relevant comparison is continuous BRUKINSA, which, of course, has much, you know, better-looking 6-year data, you know, from a patient and physician perspective. You know, we need to see how the thing evolves, but it will take time. It'll take more than 6 years to understand and establish for those high-risk patients, is this really something that's as good as and competitive with, you know, long-term continuous BRUKINSA? It'd be great if it is, but, you know, nobody can be sure of that.

Speaker #2: Well, that's not the relevant comparison; the relevant comparison is continuous Burkinza, which, of course, has much better-looking six-year data from a patient and physician perspective.

Speaker #2: So we need to see how the thing evolves. But it will take time. It'll take more than six years. To understand and establish for those high-risk patients is this really something that's as good as?

Speaker #2: And competitive with long-term continuous Burkinza use? Be great if it is, but nobody can be sure of that. At any rate, thank you so much for the question.

[Company Representative] (BeOne Medicines): At any rate, thank you so much for the question, I'd like to, you know, thank everybody for, you know, today's discussion. It really marks the close of a strong Q4, and it's a pivotal, you know, full year for Be One. I think as you just heard, 2025 was defined by really flawless commercial execution and accelerated R&D momentum across our whole business. I do believe that our performance reflects what truly differentiates Be One as a company. It's our commitment to scientific excellence, our exceptional speed, our relentless focus on developing the best long-term outcomes for all patients.

John Oyler: At any rate, thank you so much for the question, I'd like to, you know, thank everybody for, you know, today's discussion. It really marks the close of a strong Q4, and it's a pivotal, you know, full year for Be One. I think as you just heard, 2025 was defined by really flawless commercial execution and accelerated R&D momentum across our whole business. I do believe that our performance reflects what truly differentiates Be One as a company. It's our commitment to scientific excellence, our exceptional speed, our relentless focus on developing the best long-term outcomes for all patients.

Speaker #2: And I'd like to thank everybody for today's discussion. It really marks the close of a strong fourth quarter. And it's a pivotal full year for B1.

Speaker #2: And I think as you just heard, 2025 was defined by really flawless commercial execution and accelerated R&D momentum across our whole business. And I do believe that our performance reflects what truly differentiates B1 as a company.

Speaker #2: It's our commitment to scientific excellence, our exceptional speed, our relentless focus on developing the best long-term outcomes. For all patients. And on behalf of everyone here, I really want to thank the broader oncology community, the patients and families who inspire our work, the clinicians who partner with us every day, and our almost 12,000 employees all around the world who continue to raise the bar.

[Company Representative] (BeOne Medicines): On behalf of everyone here, I really want to thank the broader oncology community, the patients and families who inspire our work, the clinicians who partner with us every day, and our almost 12,000 employees all around the world who continue to raise the bar. I truly believe that together, we're how the world stops cancer, and as we enter 2026, we're more confident than ever in the opportunity ahead of us. Thank you again, everyone, for your time today, and have a wonderful week.

John Oyler: On behalf of everyone here, I really want to thank the broader oncology community, the patients and families who inspire our work, the clinicians who partner with us every day, and our almost 12,000 employees all around the world who continue to raise the bar. I truly believe that together, we're how the world stops cancer, and as we enter 2026, we're more confident than ever in the opportunity ahead of us. Thank you again, everyone, for your time today, and have a wonderful week.

Speaker #2: I truly believe that together, we're how the world stops cancer. And as we enter 2026, we're more confident than ever in the opportunity ahead of us.