Q3 2025 BeOne Medicines Earnings Call
Speaker #1: Since .
Speaker #2: Before we begin , please note that you can find additional materials , including a replay of today's webcast and presentation on the Investor Relations section of our website .
Speaker #2: I'll be . Com . I would like to remind all participants that during this call , we may make forward looking statements regarding , among other things , the company's future prospects and business strategy .
Speaker #2: Actual results may differ materially from those indicated in the forward looking statements . As a result of various factors , including those risks discussed in our most recent periodic report filed with the SEC .
Speaker #2: Please also carefully review the forward looking statements . Disclaimer in the slide deck that accompanies this presentation . Reconciliations between GAAP and non-GAAP financial measures discussed on this call are provided in the appendix to our presentation , which is posted to our Investor Relations website , along with the earnings release .
Speaker #2: All information in this presentation is as of the date of this presentation , and we undertake no duty to update such information unless required by law .
Speaker #2: Now , turning to today's call as outlined on slide three . John Oyler our co-founder , chairman and CEO will provide a business update .
Speaker #2: Aaron Rosenberg , our CFO will provide an update on our third quarter financial results and financial guidance . And liwang , our global head of R&D , will discuss our R&D and pipeline progress .
Speaker #2: We will then open the call to questions . Joining the team for the Q&A portion of the call will be Xiaobin Wu President and Chief Operating Officer , Matt Shaulis .
Speaker #2: Our General Manager of North America . And Matt Mark Lanasa , our chief medical officer for solid tumors . I'll now pass the call over to John .
Speaker #2: John .
Speaker #3: Thanks , Stan . And thank you , everyone for joining us today . The third quarter marked another strong quarter of execution from a financial perspective .
Speaker #3: Revenue reached 1.4 billion , which represents 41% year on year growth . GAAP earnings per Ads were $1.09 , which represents growth of more than $2 over Q3 of last year .
Speaker #3: And we generated over 350 million of free cash flow during the quarter . As Aaron will touch on , we strengthened our balance sheet and ended the quarter with over 4 billion in cash .
Speaker #3: Frequenza has continued its momentum with sustained US leadership , and it's now the number one BTK inhibitor globally . Conroe our next generation Bcl2 inhibitor , recently received FDA breakthrough designation in relapsed refractory mantle cell lymphoma .
Speaker #3: And we're really excited about the totality of data emerging from that molecule . Some of which we're going to highlight today . Brukinsa and our BTK cdac are the core elements of our leadership in B-cell malignancies .
Speaker #3: And they'll be on display next month at Ash , where we'll present 47 abstracts from across our heme portfolio . The quarter also yielded multiple developments across our growing solid tumor pipeline , including clinical proof of concept for multiple early stage assets , which is going to discuss in more detail later .
Speaker #3: So let me start with brukinsa . The backbone of our heme franchise Brukinsa , continued to perform exceptionally well in the third quarter , growing 51% and exceeding 1 billion in quarterly global revenue for the first time .
Speaker #3: As a result , and also for the first time , Brukinsa is now the global value share leader amongst the growing BTK market .
Speaker #3: This , of course , is a major milestone for Brukinsa and for our company . As I discussed in detail on our Q2 earnings call , the commercial success of Brukinsa is not by chance .
Speaker #3: It's the direct result of an overwhelming body of evidence that has accumulated over more than a decade . It's evidence that spans preclinical human pharmacokinetics .
Speaker #3: Head to head , clinical trials , real world data sets , and patient physician preference in the market . The evidence is remarkable for both its strength as well as its consistency .
Speaker #3: And this evidence continues to build with each new piece of data , both reconfirming and further strengthening our initial therapeutic hypothesis that brukinsa is the best BTK inhibitor at B1 .
Speaker #3: We're relentlessly focused on our goal of discovering and developing innovative medicines that deliver long term outcomes for patients . At Ash , we're presenting a 74% landmark PFS at six years for Brukinsa in first line CLL .
Speaker #3: This is from our phase three Sequoia trial . We believe that these data have set the bar for what monotherapy BTK can and should be .
Speaker #3: What they should achieve in CLL with all the caveats of Cross-trial comparisons . This is double digit better than what has been reported for other single agent btkis .
Speaker #3: At 72 months . Interestingly , this level of sustained PFS at six years is in the same ballpark as other recent data from BTK , then fixed duration regimens at only three years .
Speaker #3: Long term follow up from years three through six , when patients are not on active therapy , will be critically important to inform the future relevance of these regimens within the CLL treatment paradigm .
Speaker #3: And I think along those lines , what's also relevant about this year's Ash is what you're not seeing , given what I've just said about the importance of our long term brukinsa data in CLL , the absence of other long term follow up data from many other relevant CLL trials , such as amplify with the last data cutoff April 30th , 2024 , captivate and Elevate , where data hasn't been reported for a couple of years .
Speaker #3: Long term data are the gold standard in CLL for a reason . Because KLS , an indolent disease and it takes time to fully and truly understand how these regimens perform brukinsa delivers the level of progression free survival that patients and physicians should expect and should demand .
Speaker #3: We believe in the promise of fixed duration , but we also feel that the current Venn based options fall far short of that promise .
Speaker #3: In our view , the current options fail to satisfy the four key criteria that you see on this slide . Depth of response , sustained PFS , safety and convenience .
Speaker #3: Specifically , we have concerns related to the low MRD negativity rates and sustained PFS for AV combinations . The cardiac safety , uveitis and general tolerability for IV combinations .
Speaker #3: The long term effects on the immune system and the related additional hospitalizations due to infections of obinutuzumab use and the overall treatment burden and feasibility of use .
Speaker #3: With all of the Venn based regimens , our goal in fixed duration is simple . We aim to develop a more efficacious , time , limited regimen that does not come with caveats or accommodations , and based on the data we've generated to date , we believe that the combination of ZANU and Sono is well on its way to achieving just that .
Speaker #3: Our confidence in ZiS is based on the totality of clinical data to date , but there are a couple of key aspects in the data that we find exceptionally compelling .
Speaker #3: Here you can see the umrd rates and the time to blood MRD from our phase one trial . This was presented at our R&D day in June , and we'll provide a further update on these curves at Ash .
Speaker #3: Of all the data , our team franchises generating , these might be the most compelling to the kols that we meet . So let me explain .
Speaker #3: First , the combination of ZANU and Sono can drive very high rates of deep response . Secondly , and perhaps more impressively , it does so exceptionally quickly with kinetics .
Speaker #3: Previously unseen in other trials of drugs targeting similar mechanisms . This slide is so important that we're going to show it to you twice today , once now and once in live section .
Speaker #3: This is the type of deep response that we're looking for in a fixed duration regimen to give physicians and patients the confidence to stop therapy and to achieve positive , long term outcomes .
Speaker #3: B1 stands out as the only company with fully owned , potentially best in class assets across the three foundational Moas and CLL . Brukinsa , sono and our BTK , CDA .
Speaker #3: All three are anchored in differentiated design hypotheses and bolstered by an ever growing body of evidence . All three of the potential for the broadest utility in the class , and all three , whether as monotherapy or in combination , represents significant opportunities for patients , physicians , and for our shareholders .
Speaker #3: Together , brukinsa sono and our BTK c-dac are driving the future treatment paradigm in the $12 billion and growing global CLL market . close , I'd like to introduce what we're calling our development global Superhighway .
Speaker #3: For those of you that are newer to our story , B1 was built different early on . We recognized the vast majority of the time and cost to develop and deliver a medicine was in clinical trials .
Speaker #3: We felt that such a critical component of the biopharma supply chain should be a core competency , rather than something that is outsourced to a CRO .
Speaker #3: We saw the synergies that were possible by vertically integrating Before I manufacturing with an industry leading clinical organization , and we know from experience how hard this can be for a small company .
Speaker #3: So fast forward 15 years and we're proud to have built a global organization of nearly 6000 colleagues across these two areas . Clinical development and manufacturing .
Speaker #3: And in today's hyper competitive , costly and complicated era of drug development , we really believe that this global superhighway is unique to B1 , and it's critical to generating superior returns on R&D , investment .
Speaker #3: To close , we're in the midst of an exciting milestone rich period for both our team franchise and our solid tumor pipeline . By the end of 26 , we expect the initial global approval and launch of Sono and potentially pivotal data for our BTK , Cdac , our internal clinical team will be running more than 20 phase three trials .
Speaker #3: We anticipate more than ten proof of concept data readouts , and our research organization will advance around ten new molecular entities into the clinic .
Speaker #3: Three of which will be in heme and not just in CLL , but broadening our portfolio to help patients in other areas . Now I'll pass it over to Aaron to provide the financial update .
Speaker #3: Thanks , John .
Speaker #2: In the third quarter , we sustained business momentum across our product portfolio with another quarter of solid execution by our global commercial teams .
Speaker #2: Product revenue reached 1.4 billion in the second quarter , representing 40% year over year growth . Brukinsa global revenues eclipsed 1 billion for the first time in a quarter , growing 51% , driven by strong performance across all geographies .
Speaker #2: As John mentioned , Brukinsa is now the leading BTK globally in the US . We grew Brukinsa volume by approximately 40% versus Q3 2024 , driven by the quality and differentiation of our long term clinical data across all patient types .
Speaker #2: The 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 .
Speaker #2: Meanwhile , Tevimbra reported a 17% increase , reflecting continued market leadership in China , albeit in an increasingly competitive market environment . This growth was supplemented by early contributions from launch markets .
Speaker #2: Our insights In-licensed products also showed continued strength , growing 17% year over year , driven by growth of 31% from the Amgen In-licensed asset portfolio .
Speaker #2: We continue to see solid execution as we look at revenue from a geographic dimension . The US remains our largest market , generating 743 million with year over year growth of 47% .
Speaker #2: China revenue totaled 435 million , a 17% increase supported by Tevimbra and Perkins's market leadership and growth from our In-licensed assets . Europe contributed 167 million , with 71% year over year growth .
Speaker #2: As we continue our launch trajectory with Brukinsa , with increased share across all major markets and rest of world markets grew 133% , driven by market expansions and new launches .
Speaker #2: Now turning to the other components of our GAAP PNL gross margin improved to 86% from approximately 83% in the prior year . This improvement reflects the benefit from favorable product mix , price , and product cost efficiencies , offset by period costs related to repositioning of our manufacturing capacity .
Speaker #2: Operating expenses grew by 11% , totaling 1.1 billion . As we are investing with discipline to support our commercial growth and rapidly advance our innovative pipeline .
Speaker #2: I thought it worth noting that the Q3 2024 base for R&D has higher expenses for both business development milestones , plus approximately 25 million in accelerated depreciation charges .
Speaker #2: Together , this has the effect of depressing the year over year growth rates in our Q3 2025 R&D expense , which you can observe to a degree on the non-GAAP PNL slide , which excludes depreciation .
Speaker #2: We continue to invest assertively to advance our most promising development candidates . Income tax expense totaled 22 million for the quarter , an altogether net income reached 125 million , representing diluted earnings per Ads of $1.09 .
Speaker #2: Our non-GAAP PNL includes adjustments for typical items with a full reconciliation provided in the appendix . non-GAAP net income reached 304 million , reflecting an increase of 252 million compared to the previous year .
Speaker #2: This performance translates to diluted non-GAAP earnings per ads of $2.65 for the third quarter . The third quarter saw a progress in our priority of balance sheet strength as a competitive advantage .
Speaker #2: In August , we entered into a transaction to monetize our global industrial royalty rights , generating 885 million in cash in the quarter .
Speaker #2: While allowing us to participate in the potential upside with the asset . The royalty pharma agreement is accounted for as a liability and therefore we will continue to recognize the full and royalty in other revenue as it is earned while simultaneously amortizing the financing liability in interest expense .
Speaker #2: Please see our 10-q for a full description of the notable accounting for this transaction . And with our meaningful top line growth with margin expansion , we've seen a notable increase in free cash flow generation to 354 million in this quarter .
Speaker #2: Cash generation is the key metric of business sustainability . And we are very pleased with our progress on this dimension . All in Q3 ending cash and cash equivalents totaled 4.1 billion , an increase of 1.3 billion versus Q2 .
Speaker #2: Moving to our 2025 financial guidance . Given our continued execution , we are updating our full year revenue guidance to be between 5.1 billion and 5.3 billion .
Speaker #2: Our gross margin guidance is unchanged , remaining in the mid to high 80% range , and we are updating our operating expense guidance to be between 4.1 billion to 4.3 billion .
Speaker #2: We remain committed to achieving positive GAAP operating income , and we expect to generate positive free cash flow for the year . Overall , we are pleased with our execution through the first three quarters of 2025 , and we remain focused on full year delivery across all financial performance measures .
Speaker #2: Now , while early and staying away from providing detailed guidance , I'd like to provide some perspectives on 2026 . As you consider your models for the fourth quarter of 2025 and into the first quarter of 2026 , I thought it would be useful to remind you of the seasonality patterns in the US of the BTK class .
Speaker #2: This includes factors such as typical inventory increases at the end of the year , followed by normal drawdowns in January . Also , just like this year , Q1 2026 will have fewer shipment days versus a typical 13 week quarter .
Speaker #2: This is simply the nature of the calendar , but is something that should be considered in quarterly phasing . And while we remain committed to margin expansion across our planning horizon , the pace of improvement will be measured in the near term to ensure we invest .
Speaker #2: We are investing to maximize the value of our late stage pipeline opportunities . We look forward to providing our detailed 2026 guidance on our Q4 earnings call in February , and with that , it seems like an excellent time to pass it over to Lee , who will share more progress about our pipeline .
Speaker #2: Thank you . Aaron . Hi everyone . Thanks for joining us today .
Speaker #4: Let me start with hematology . Nearly 50 abstracts , including six orals from our hematology portfolio have been accepted for presentation at Ash this year .
Speaker #4: This is a tremendous validation of the strengths and the depth of our science , our highlight some of those key data later in my presentation .
Speaker #4: Importantly , song has now received FDA Breakthrough Therapy designation for mantle Cell lymphoma , while actively working on its first filing around the globe .
Speaker #4: And our BTK Degrader program has just started the phase three head to head trial versus the industrial factory cell patients . A major step toward a transforming this space on the solid tumor side .
Speaker #4: Our momentum continues to build . We have achieved proof of concept for several innovative programs , including our Cdk4 inhibitor b7-h4 , ADC , PND five inhibitor , and Gpc3 four one bispecific should be noted .
Speaker #4: Most of these assets have been in the clinic for less than 18 months, and some less than one year. This is the level of efficiency and the focus we aim to deliver across the portfolio.
Speaker #4: We aim to initiate a phase three trial in first line BC . In the first half of 2026 . On the Non-oncology side , our for select program achieved over 95% ROI for protein degradation in healthy volunteers , skin tissue .
Speaker #4: A clear PD proof of concept . We have already initiated a phase two trial in rheumatoid arthritis over the past few years , especially in the last 24 months , we have dramatically increased our output from the discovery engine .
Speaker #4: In that time , we have advanced 16 new molecule entities into the clinic , including 13 from our internal research team , among them .
Speaker #4: Four molecules have already achieved clinical proof of concept supporting pivotal study plan . This does not count our quality grade program achieving tissue PD , POC across the portfolio .
Speaker #4: Our programs have completed R&D , enabling studies in a medium of just ten months . We are ahead of industry benchmarks even more impressively , in 2024 and 2025 , we have completed over 170 dose escalation cohorts with a median time of only seven weeks .
Speaker #4: This level of speed and precision is what defines B1 . Our ability to move fast , execute flawlessly and turn innovation into impact .
Speaker #4: Moving on to our solid tumor portfolio , an area we're very excited about and where we feel increasingly confident as several programs advance toward registration .
Speaker #4: This confidence is built on strong , evolving clinical data . First , our CDK four inhibitor program is moving forward quickly . We plan to initiate a phase three trial in first line formal receptor positive breast cancer .
Speaker #4: In the first half of 2026 , driven by emerging strong efficacy and safety data from our expansion cohorts . In addition , we deprioritized the phase three development in the second line post Cdk4 six setting .
Speaker #4: Due to the evolving competitive landscape in that context, we decided for competitive reasons to delay the disclosure of our late-line data.
Speaker #4: Since it is also relevant to our dose selection in frontline . Second , our B7-h4 ADC program has completed dose escalation and we are now conducting dose optimization studies with particularly encouraging responses seen in gynecologic , surgical and triple negative breast cancers .
Speaker #4: Third , our findings have just stands out with potentially best in class features , including potency , selectivity and most importantly , brain penetration .
Speaker #4: Based on the emerging phase one data , we are now accelerating this program into frontline lung and frontline pancreatic cancer . And finally , our GPC three for one bispecific has delivered a pleasant surprise while seeing very exciting signals as monotherapy in its first in human study in heavily pre-treated HCC tumors .
Speaker #4: Altogether , this is a portfolio that is maturing quickly and backed by early clinical momentum . And we are incredibly energized by what's ahead for our other solid tumor assets .
Speaker #4: While continue to execute and party's programs with the strongest potential . Our ADC , EGFR mathematical and the Fgfr2 ADC programs are all showing encouraging early signals while continuing advancing the CDK two inhibitor EGFR .
Speaker #4: KD and pancreas inhibitor programs through phase one dose escalation studies . At the same time , based on the current data and the broader competitive landscape , we have made the strategic decision to realign the CDC and Pro 15 programs within the portfolio .
Speaker #4: This really reflects V1's disciplined development strategy, focusing our resources on programs with clear differentiation and advancing them quickly to the most important value.
Speaker #4: Inflection points . Clinical POC , where we can make data based decisions . This is how we continue to build a high quality , high velocity portfolio in solid tumors .
Speaker #4: Moving on to our hematology portfolio , our strong program is shaping up to be a potential best in class BCL two inhibitor , offering great efficacy , improved safety , and better convenience compared compared with the first generation agent class one .
Speaker #4: Now , in the process of filing for approval in relapsed refractory mantle cell lymphoma globally . And we look forward to sharing good news very soon in this space .
Speaker #4: The most critical indication for so long is still , we have completed enrollment in our phase three trial . Comparing that fixed duration regimen versus V0 earlier this year .
Speaker #4: In addition , we plan to launch another global phase three study in the first half of 2026 , comparing these versus AB , I to establish CS as the best oral fixed duration regimen in treatment .
Speaker #4: Naive CL and finally , in 2026 , we also plan to initiate a phase three in second line plus multiple myeloma . Exploring solar based triplet combination .
Speaker #4: Next , a quick update on the ASP designation for solo . What you see on this slide are two selected abstracts published earlier this week on monotherapy , starting with mantle cell lymphoma in 103 relapsed refractory patients who had prior BTK inhibitor and anti-cd20 therapy so achieved an overall response rate of 53% , with a median progression free survival of 6.5 months and a median duration of response of 15.8 months .
Speaker #4: This results look favorable compared to historical data in a similar population . Even when van was used as three times of its clinical proven dose .
Speaker #4: On the other side , the table on the right shows the data from a single ARM study of 100 patients who oppose BTK inhibitor and post chemo immunotherapy .
Speaker #4: Have sonar achieved a response rate with 19% complete responses ? Both the efficacy and safety profile look quite favorable relative to vans previous published data .
Speaker #4: In a similar population . Altogether , this this results in strong potential to be the best in class BCL two inhibitor in hematological malignancies .
Speaker #4: In addition to the Solo monotherapy update , we are also presenting new data on the Sono combinations with ZANU and all with Obinutuzumab in CLL .
Speaker #4: At this year's apps for the Zs combination , we have more mature data as additional patients have gone through treatments . The term monks UMD rate has achieved has reached 92% and the most impressively , with a median follow up of 27 months to date , no patients have progressed in the 320mg cohort , which is truly remarkable for the ash presentation .
Speaker #4: We have another data cut with additional months of follow up showing a consistent results in terms of the safety , the profile continued to show a clear advantage compared to other fixed duration regimens .
Speaker #4: And in terms of convenience , we're very optimistic that for the vast majority of patients , only one . Clinical visit during the ramp up will be required for that .
Speaker #4: After reading . This is a meaningful improvement for both patients and physicians . What's most exciting about this combination is the kinetics of the UMD achievements , which John showed you earlier , as shown on the left , the median term to UMD with the Zs combination was only around four months after starting the combo .
Speaker #4: And importantly , this is independent of IgG mutation status by about one year of combination therapy . That's the dashed line on the graph .
Speaker #4: The vast majority of patients achieved UMD , in contrast with the IV combination on the right , the median term to unmarred is 16 months .
Speaker #4: For mutated and ten months for unmutated patients . And the at the one year mark of combo treatment . Many still remain MRD positive .
Speaker #4: So overall , we believe that combining two potentially best in class agents , Daniel and Solo , may provide the only true fixed duration options that delivers optimal efficacy , safety and convenience for patients with CLL .
Speaker #4: In a reasonable timeframe . Now , the updates on our BTK , Cdec , BGB IgG 166731673 is the most advanced program of its kind in the clinic , with clear best in class potential .
Speaker #4: We have initiated a head to head phase three trial against the Pirtobrutinib in the potential , the potentially pivotal phase two study in relapsed refractory CLL is expected to have a data readout in the first half of 2026 .
Speaker #4: We're also planning a fixed duration combination phase three study with Sono in relapsed refractory CLL and potentially pivotal two R in water storm Macroglobulinemia has been initiated .
Speaker #4: We will also share new BTK select data at this year's Ash meeting . The table on the left shows the results published in the abstract 16673 demonstrated an overall response rate of 86.4% , with median 18 month follow up .
Speaker #4: The 12 month progression free survival is now mature at 79% . A very favorable profile compared with ibrutinib in the similar patient population .
Speaker #4: We also reported new data in the transformation on the Waldenstrom macroglobulinemia in vectors . The Orr was 52% , with nearly 10% complete responses in water storms .
Speaker #4: We saw an 83% with a 26% vg PR rate . Altogether , these data further strengthens CDA position as a potentially best in class BTK degrader across multiple B-cell malignancies .
Speaker #4: The robust clinical activity we observed is consistent with the preclinical data package with regard to that potency , as shown on the left , we observe similar DC 50 and DC 90 values for one , six , seven , three , and the new molecule in head to head BTK degrader assays in both human whole blood cells and B cells , and we believe 1673 holds a clear advantage in terms of BTK mutation coverage , as shown on the right .
Speaker #4: Except for a for ad mutation , 1673 can cover all other BTK mutants , whereas we observed the nearest molecule showed two resistance hot spots and assigning for 77 and glycine for 80 residues .
Speaker #4: The broader mutation coverage of 1673 . Further reinforces its best in class potential , and its ability to deliver potentially more durable responses for patients .
Speaker #4: Together , sorrel and 1673 highlighted the depth , quality , and momentum of our hematology portfolio , advancing rapidly toward multiple late stage milestones and transformational opportunities in the years ahead .
Speaker #4: Finally , I'd like to share a few key milestones with tracking for the remainder of this year and into 2026 , focusing on the ones I have not mentioned earlier .
Speaker #4: First , for cancer , the phase three interim analysis readouts for the mangrove study in Treatment-naive mantle cell lymphoma has been delayed from the second half of this year to the first half of next year due to the slower than anticipated event rate in addition , we are anticipating a accelerated approval for Soolantra class in Russia , mantle cell lymphoma and the kill in China early next year .
Speaker #4: Important milestones . As we continue to broaden access for patients globally . Turning to our early stage pipeline , we are anticipating pox for ADC before the year end and the other assets in 2026 .
Speaker #4: We look forward to sharing more data in future updates . And with that , I will turn the call back to John .
Speaker #3: Thanks . Lai . We'll now open the call to Q&A . Please limit the number of questions to ensure we have time to hear from as many attendees as possible .
Speaker #3: Operator , please go ahead . .
Speaker #5: 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 .
Speaker #5: When you are called on , please unmute your line and ask your question . We will now take a minute for the queue to assemble .
Speaker #5: Our first question will come from your own Werber with Cohen and company . You may now unmute your audio and ask your question .
Speaker #6: All right . Well , terrific . Hopefully you can hear me .
Speaker #3: Yes .
Speaker #6: Excellent . Congrats . I really nice quarter . I'm going to violate the rule right away . Just two quick questions . Number one Brukinsa is the global leader .
Speaker #6: You're obviously a little bit behind in Europe in terms of when you launched any sense and when new territories are coming in to accelerate that .
Speaker #6: And then secondly , live for the CDC data in the first half of next year in CLL for the potential support , accelerated approval , can you give us a sense of what to expect there and sort of how mature is the PFS going to be ?
Speaker #6: Thank you .
Speaker #3: Great . So do you want to start .
Speaker #2: Yeah .
Speaker #7: In Europe we grow for Brukinsa tremendously . So close to 70% . And we notified in Europe in some countries like Germany Austria amplify launched and we don't see much excitement among the FCP , Effcts and the company may actually be switch the mono .
Speaker #7: Acala to amplify , but so far we have not seen we see some some prescription , but not extremely large prescription . Therefore , the total acala in Europe , if you see the number is flattened .
Speaker #4: SOE regarding to the CDC data and this is a single ARM study , so likely to be based on the Or as well as the door .
Speaker #4: So depending on the further discussion with agency as usual , it will be probably about 12 months after the last patient year .
Speaker #1: Great .
Speaker #3: Next question .
Speaker #5: Our next question comes from Wendy Benjamin with citizens Bank . You may now unmute and ask your question .
Speaker #6: Hey good morning guys .
Speaker #8: Thanks for taking the questions . And congratulations on another amazing quarter . We'd love to just focus on the earlier stage pipeline a little bit .
Speaker #8: You had mentioned proof of concept data . Can you maybe provide a little bit more color as to , you know , what you're seeing with with some of these other assets ?
Speaker #8: And should we be thinking that all these would likely progress to phase three trials moving forward ? And if I can sneak one in , is there a teaser you could provide regarding the ten new molecular entities that you're filing next year ?
Speaker #8: Is there a novel target that you're most excited about ? Thanks .
Speaker #3: God , we wish that science worked in a way where everything worked , but why don't you answer that question ?
Speaker #4: Probably refer to Mark because he's in the front line for all this data Mark .
Speaker #9: Thank you . Lee . Thank you Renee . What I would say is that for all of our early programs , we established very clear criteria of what success looks like based upon the preclinical data .
Speaker #9: What what are we looking for in terms of PK , PD , safety and ultimately efficacy ? If you think back to the slide , that Lai showed , where he talked about where the different programs stand , I think you could think about that as some of those programs are meeting all of those criteria .
Speaker #9: The for of Cdk4 , Prmt5 , B7-h4 , Gpc3 , and therefore we're actively planning acceleration to phase three studies in program growth .
Speaker #9: Others , we continue to wait for data . And we believe that we'll have the data to make the final determination for most of the programs in the first half of 26 .
Speaker #4: Yeah . Then in terms of the new entities , we're going to bring to the clinic next , you know , I'm going to use the Gpc3 of one BB as an example .
Speaker #4: To be honest , among the program we took into clinical last year , this certainly was not the most exciting one for us based on the pre-clinical data , but it's certainly we are very pleased with what we have seen in the clinic today .
Speaker #4: So I'm not going to say which one is the most exciting one for us in the next year , but we're certainly looking forward to bring more .
Speaker #4: I just want to emphasize one more thing . What you have seen from B1 is really just the beginning of what you can see from our really prolific discovery engine .
Speaker #3: All right . Next question please .
Speaker #5: Next question comes from Andrew Behrens with partners . Please unmute your line and ask your question .
Speaker #10: Hi . Thanks . And let me get my congratulations on the progress and execution for the quarter . I think with your question , you answered one of the ones I had because Astra in their earnings release today , did highlight the fixed duration and amplify Regiment getting traction in Europe .
Speaker #10: But it sounds like you guys have not seen a lot of that yet . So I just wanted to confirm that that that's what you had said .
Speaker #10: And then a question on the Prmt5 program . It's still expected by year end . Just wondering , I know you mentioned the first line , Pdac and non-small cell lung cancer opportunity .
Speaker #10: Just wondering how you think of combination partners for those settings . Thanks .
Speaker #7: Yeah , I confirm and the so Acala market share . And also the revenue in the last three three months . Pretty stable in Germany and not increasing of course , with amplified approval and fixed duration of amplified will be added to the respective guideline .
Speaker #7: This may give some . Yeah , some sort of plus for the overall in Europe and also in Germany . The Acala total data flattening .
Speaker #3: Mark , do you want to take the second part .
Speaker #9: So we , as you heard , are very excited about our prmt5 molecule . That's only been in the clinic since January of this year .
Speaker #9: But given its high potency in CNS penetration , we're now seeing objective responses across multiple tumor types , including both lung and pancreatic cancer , as well as additional tumor types .
Speaker #9: And critically , given its high selectivity , we're also seeing a very favorable safety profile that we think will enable combinations which will be key to unlocking the potential of this mechanism , and therefore we're advancing into frontline to combine with current standards of care .
Speaker #9: We do not yet have the data , but it is our expectation that we'll be able to combine with chemotherapy and PD one in non-small cell lung cancer and standard of care chemotherapy and frontline pancreatic cancer .
Speaker #9: And we'll look for similar development opportunities in early lines of other tumor types with frequent mtap deletion .
Speaker #10: Okay . Thanks . Andy . Any belief that maybe combining with some of the selective agents might work in certain mutations like the mutations .
Speaker #9: So we are very interested in RA biology . Our Kras molecule is advancing through phase one . We discussed at R&D day a commitment to bring multiple additional Ras targeting molecules into the clinic .
Speaker #9: So certainly in pancreatic cancer , for example , we will ultimately look to combine Prmt5 with Kras . So again , the aspiration given potency and selectivity is that we should be able to combine with whatever is the appropriate additional therapies for that patient given the disease state and any other concurrent mutations .
Speaker #10: Okay . Thank you and congrats again .
Speaker #5: Thanks . Next question comes from Yigal with Citigroup . Please go ahead with your question .
Speaker #11: Hi . Can you hear me ?
Speaker #3: Yes .
Speaker #11: Okay . Great . This one is for for Lai or Mark . Maybe . Could you give a little more detail on the design of the Cdk4 phase three ?
Speaker #11: In terms of what you can say at this point about the control arm , the size of the study , anything on the powering , and also what are the doses that are the final contenders for that study ?
Speaker #3: Please go ahead . Mark .
Speaker #9: Yeah . Thank you . Yigal . So at R&D day , we talked about the three dose levels that are being explored in our expansion phase .
Speaker #9: Two 4406 hundred . We've completed enrollment of our frontline cohorts . And we're very excited with the data as they're coming in . We are seeing a high response rate that we think , well justifies initiation of a phase three study .
Speaker #9: The core hypothesis with the molecule is that having a more selective Cdk4 inhibitor will be superior to currently available Cdk4 six inhibitors . Therefore , we're intending a head to head study .
Speaker #9: We're still waiting for data to make final decisions around study design , size , and powering , but we certainly should be able to share those details in the near future as we move towards a phase three study .
Speaker #9: Start by the end of the first half of next year .
Speaker #11: Okay , thanks . And then I think I mentioned the new phase three Zs versus Avi . I was just wondering regarding the rationale around that .
Speaker #11: I was under the impression you kind of already knew the conclusion there that Zs was better . So I'm just curious as to as to the rationale for that additional investment to further prove that point .
Speaker #12: Please go ahead . Line .
Speaker #2: Yeah .
Speaker #4: Thank you for that question . And we agree with your comments . But we felt this is important to establish Zs as really the best oral .
Speaker #4: Fixed duration regimen . So , you know , we picked the one which likely will be approved as soon by FDA on the Avi regimen .
Speaker #4: We do have a lot of confidence in them for this particular study .
Speaker #3: Yeah , I think if I just elaborate a little bit on that , you know , we encourage everyone to look frequently at the CLL data , especially the long term data that we've presented .
Speaker #3: But still , people will say , well , there's no head to head study against acala versus Zanu and still people will discount , you know , the body and wealth of information that's there .
Speaker #3: And I think when you look at the data and you talk to the top kols , I think at this point with this long term data , it's very clear .
Speaker #3: But nonetheless , there's always someone who says there's not direct head to head . And I think this commercially is helpful and it's helpful to bridge that , you know , information gap help educate people more quickly .
Speaker #3: I mean , just , you know , when we're looking at , you know , that space , you know , the long term data , it's meaningfully different with all the cross-trial comparisons .
Speaker #3: As we said , it's double digit different . Look at the PFS , look at the OS data . It's impressive . But we still get that comment .
Speaker #3: You know , in a small portion of the population around the globe . So we just think it's important to do this so we can ensure that everyone is getting the best medicine and the best regimen .
Speaker #3: So , you know , we're committed to doing it .
Speaker #11: Great . Thank you .
Speaker #5: Our next question comes from Leonard Timashov with RBC . Please go ahead with your question .
Speaker #13: Hey , guys . Thanks for taking my question . I just want to ask maybe on some of the commercial dynamics you're seeing outside of the early line setting in CLL , maybe more on the relapsed refractory setting .
Speaker #13: How's Brukinsa share holding up or growing there ? And then ultimately , how would you expect the mix of a degrader brukinsa and covalent inhibitors to play in the future there ?
Speaker #13: Thanks .
Speaker #12: Sure . Matt , please . Sure . Happy to address that . Yeah . We continue to see strong new patient start share .
Speaker #12: You know across the lines of therapy including in that relapsed setting . And then as we've discussed in the past , we're really confident in our overall CLL franchise leadership strategy .
Speaker #12: You made reference to the multiple mechanisms that are in our portfolio . And as you've heard from John , you know , we continue to have confidence in our BTK mono due to our head to head superiority with another BTK and our best in class profile , including PFS , safety and tolerability .
Speaker #12: And in the long term setting that John mentioned , we also see an opportunity for therapy that will include ZANU plus , we've spoken before about the requirements for therapy .
Speaker #12: There , and we're confident in a really strong MRD safety and tolerability profile , but also in the convenience that we can bring to to that regimen .
Speaker #12: So of course , we see the future opportunity for fixed duration with ZANU plus . But right now we're confident in monotherapy . Of course , while when it comes to the degrader , we see a clear opportunity there in later lines of therapy , I'm sure you're familiar with resistance mutations that can happen in in those earlier lines .
Speaker #12: And we have the confidence to do a head to head superiority study for the Degrader versus pure do . So we see a strong opportunity across patient types and across lines of therapy in CLL .
Speaker #3: Next question please .
Speaker #5: Our next question comes from Sean Lehmann with Morgan Stanley . Please go ahead with your question .
Speaker #14: Good morning , everyone , and hope you're all well . Just to go back on the Cdk4 inhibitor , you know , just to maybe throw some meat on the bones around , you know , the decision not to pursue later lines and to go for first line and then also just to confirm , you know , are we still going to see some data at San Antonio and , and what do you hope to present at that forum ?
Speaker #12: Thank you . Mark .
Speaker #9: Yeah . Thank you . Thank you very much , John . Yeah . So again , what we're seeing in our expansion cohorts is a very strong emerging response rate .
Speaker #9: We are waiting for data maturity now in the context of the strength of that data . And also importantly , the context of emerging data externally .
Speaker #9: So there are a number of new agents that are leading to both fragmentation in the second line as well as an increasing bar for success in second line .
Speaker #9: We always viewed the second line opportunity as a transitional opportunity for this molecule , and the key study as the frontline study . So given this external dynamic and our strong internal data , we made the decision to deprioritize second line into accelerate frontline .
Speaker #9: Again , we're very much looking forward to that study . Concurrently . We then subsequently made the decision that we would not share the second line data at this year's San Antonio .
Speaker #9: We think those data are relevant to our dose level selection for phase three and frontline , and we therefore will not have data for this molecule at the San Antonio .
Speaker #9: But look forward to sharing data at a future venue that will , shall we say , substantiate our plans for the phase three study and frontline .
Speaker #14: Great . Thank you . And one quick follow up just on . There's any plus versus V plus . So phase three sort of recruited earlier this year .
Speaker #14: What sort of the signpost pathway or the map going forward in terms of , you know , future announcements around that , that trial lie ?
Speaker #3: Do you want to answer that , please .
Speaker #12: Yes , certainly .
Speaker #4: In that particular study , it's a . Events driven studies , as you can imagine , with the control arm using the Vo .
Speaker #4: It's really good therapy as well . So it will take a little bit of time to get into the readout . But at the same time , we're also monitoring the umrd rate .
Speaker #4: This will be something we can probably take a look at .
Speaker #14: Wonderful . Thank you .
Speaker #12: Great .
Speaker #5: Our next question comes from Jesse with J.P. Morgan. Please go ahead with your question.
Speaker #15: Hey , guys . Good morning . Thanks for taking my question . I had one on the EGFR targeted assets . I guess what in particular makes you say that ?
Speaker #15: The EGFR C-met C-met product goes in the promising bucket , whereas the EGFR cdac is in the still exploring bucket . Is that based on clinical data or if not , can you just elaborate on kind of how you segmented those ?
Speaker #15: Thank you .
Speaker #3: Sure . Mark , please go ahead .
Speaker #9: Sure . Thank you Jess . So we have a number of different EGFR targeted therapies that are moving forward . And as I mentioned earlier , for each program , based upon the preclinical evidence , we have expectations of what we would like to see for the molecule initially , in terms of pKa and safety .
Speaker #9: But ultimately in terms of efficacy . So what we're seeing from the EGFR trispecific , though it's very early days in dose escalation , is that we are seeing clinically meaningful responses with that agent , with the EGFR degrader , we continue through dose escalation .
Speaker #9: We've had some tumor regressions . We're happy with the PK and the safety profile . We simply need more data maturity . It's important to highlight that these are two totally different mechanisms of action and therefore our expectations for what we would expect from each molecule are somewhat different .
Speaker #15: Thank you .
Speaker #5: Our next question comes from Klara Dong with Jefferies . Please go ahead with your question .
Speaker #16: Hi . Good morning . Can you guys hear me ?
Speaker #1: Yes .
Speaker #3: Yes , we can hear you . Now we can't hear you .
Speaker #16: Can you still hear me ?
Speaker #1: Yes .
Speaker #12: Okay ,
Speaker #16: Okay . Great . Congrats on the quarter . And thanks for taking our questions . So you talk about the seasonality for the entire TKI class .
Speaker #16: So I just wondered how the seasonality dynamics differ across key regions in the US , Europe and the rest of the world as well .
Speaker #16: And then just looking at the timeline for solo and the BTK , DAC entering the market is expected to file for MCL in the US this year .
Speaker #16: And BTK C-dac has could have a pivotal readout next year in CRL . So if is this the right understanding that it potentially BTK see that can be approved first in CML in the US ?
Speaker #16: And how do you anticipate this influencing physicians sequencing strategy across B-cell malignancies , especially CLL ? Thank you .
Speaker #3: So , Aaron , going to . lie .
Speaker #2: Great . Thanks for the questions Clara . So as I said in my prepared remarks , I just wanted to reinforce , as you think about your models , the seasonality patterns , this is really a focus in the US where we typically do see inventory builds across the sector in the fourth quarter , and then that unwinds to a degree in the first quarter .
Speaker #2: And then we we did reference back to the same calendar issues that we experienced in 25 . Also in 26 globally . You see that to a lesser effect .
Speaker #2: You know , in our in our business in China , Q4 is typically a relatively lighter quarter by comparison . But given the magnitude and import in terms of percentage of revenue for Canada in the US , we thought it was really important to highlight , as you think about rolling over your models from 25 into 26 , so I can hand it over to Lai .
Speaker #2: Yeah .
Speaker #4: You're correct . In terms of in the US , as well as probably us out of CD is likely to get the seal of approval ahead of the sorrow .
Speaker #4: But that's not the case in China . In China , we're already filed the the sonographer , the CSO , which will also anticipating approval early next year in terms of sequence of the therapy .
Speaker #4: You know , we view the CDC can provide a really broad coverage in terms of patients who had a BTK inhibitor , as should actually involve the slide in today's presentation .
Speaker #4: This really covers pretty much everything except maybe one mutation . So we do believe this is probably at this moment based on the level of evidence is positioned very well in the later line therapies .
Speaker #4: After the covalent BTK inhibitor .
Speaker #16: Thank you .
Speaker #5: Our next question comes from Michael Schmidt with Guggenheim Partners . Please go ahead with your question .
Speaker #8: Oh , hey , thanks .
Speaker #17: For taking my question . I just had another bigger picture . Question around seal market . As you noted in the slides . I mean , it sounds like the amplifier regimen has , you know , modest uptake , but fixed duration treatment will clearly be part of the HCL treatment landscape .
Speaker #17: Longer term , including your own combination . And so I was just wondering how you think about how that might impact the overall size of the CRL market .
Speaker #17: The BTK inhibitor market , longer term . And then just a clarification on seasonality . Aaron , I know you made some comments around inventory in stocking at the end of the year , but then when I look at guidance , it seems like the top line , the the higher end , the top end of the range for revenue could be achieved with almost only flat Q and Q growth .
Speaker #17: And so I was just wondering if there's anything else going on in for Q that we should be aware of .
Speaker #3: So maybe I'll start with , you know , quick answer around that . You know , as I laid out earlier in this , you know , long term PFS really matters .
Speaker #3: You know , six years of follow up for data matters . These are cancer patients and you don't want progression . You know , there's no area outside of HCL .
Speaker #3: I've seen where people talk about let's take a regimen where you give up years of milestone PFS . You just don't see that .
Speaker #3: Whether it's a current event based , fixed duration treatments or other btcs or Puerto really all options beside chemo , they look pretty decent at 2 to 3 years and this just isn't enough time to understand the durability and the outcome for patients .
Speaker #3: Brukinsa consistently shows best long term patient outcomes in CLL . It's why it's the standard of care , and it's why it's the global leader .
Speaker #3: The more follow up we show , as we're doing it , ash , the more differentiated it looks . The six year data in CLL in first line and second line , and in all high risk subgroups .
Speaker #3: The story is the same . The best long term outcomes for patients at six years follow up 74% PFS rate for Brukinsa in first line CLL .
Speaker #3: When you Covid adjust this at 77 , our OS is 84% 88% Covid adjusted and elevate a PFS is 62% and their OS is 76% .
Speaker #3: At the same time period . In second line and deletion £0.17 it's the same story , unparalleled median PFS from alpine . And our Sequoia deletion 17 B data shows that Brukinsa works very well in high risk patients .
Speaker #3: It's just not the case with the other options . And we're still reporting our follow up data because it tells the story . Where is the other data ?
Speaker #3: Where is the long term data from elevate ? Where is it from captivate . Where is it from ? Amplify . It's very noticeable .
Speaker #3: It's not being reported . And you know , with respect to perto , it's 18 months of follow up in second line CLL .
Speaker #3: It's not even close to being long enough . And as we've mentioned , you know , 2 to 3 years , you just can't differentiate yet .
Speaker #3: And I think from that perspective , we're extremely confident in both the short term and when we talk about long term , the really exciting thing is this desire to have fixed duration treatments .
Speaker #3: It's a great thing if you can get there . And so far it does look like Sdx is going to be unlike anything we've seen yet .
Speaker #3: It's too early to be sure there's not enough long term follow up data for that either , but the early data looks noticeably different than anything we've seen before , so we're really , really excited about that .
Speaker #3: Now . Maybe I'll jump to Erin to answer some of the other parts of that question .
Speaker #2: Yes , thanks . Obviously , there's tremendous opportunity across the franchise as we think about where we're participating today in a 12 billion and growing market .
Speaker #2: Whether you look at it from either BTK space or overall CLL space to your question on the guidance , you know , we did reinforce the seasonality , really to make sure we support , you know , dialing in your modeling in that regard , given the history , we feel really confident on our execution over the course of the year .
Speaker #2: You know , as you referenced , we've taken up the bottom of our range from where we started . You know , we started the year at 4.9 to 5.3 , and now we're at 5.1 to 5.3 , showing increased confidence .
Speaker #2: And really , the great execution from our local teams , you know , as you said , if you annualize the current quarter run rate and you think about the next quarter , we feel that the range that we've provided is certainly within our expectations .
Speaker #2: You know , the import of the seasonality comment is really a specific to the United States . And we want to make sure that that perspective is really incorporated .
Speaker #2: Thank you .
Speaker #5: There are no further questions at this time . I will turn the call over to John Oyler for closing remarks .
Speaker #3: All right . You know , thank you all . I would like to point out that a few weeks ago , B1 celebrated our 15th anniversary as a company .
Speaker #3: It's very hard to believe that in this relatively short period of time , we've been able to become one of the leading oncology companies in the world .
Speaker #3: I'd really like to think that this is because , as you heard today , we're driven by scientific excellence , exceptional speed and a relentless drive to provide the best long term outcomes for patients .
Speaker #3: And on behalf of everyone here at B1 , I'd really like to thank the broader oncology community , including the patients , their families , the clinicians , our employees , and all of you who have been with us for the journey .
Speaker #3: We truly believe that together , we are how the world stops cancer and we're just getting started . So thank you again for your time today and your thoughtful questions .