Good day everyone. Welcome to B1 Medicine's Q3 2026 earnings call webcast. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question and answer session. At this time, I would like to turn the call over to the company.

Hello and welcome. Thanks for joining us today. I'm Dan Maller, Head of Investor Relations at V1 Medicines. Before we begin, please note that you can find additional materials, including a replay of today's webcast and presentation, on the Investor Relations section of our website, ir.v1medicines.com. I would like to remind all participants that during this call, we may make forward-looking statements regarding, among other things, the company's future prospects and business strategy. Actual results may differ materially from those indicated in Thank you for joining us. Now turning to today's call as outlined on slide three. John Oyler, our co-founder, chairman, and CEO, will provide a business update. Aaron Rosenberg, our CFO, will provide an update on our third quarter financial results and 2026 financial guidance. And Lai Wang, president and global head of R&D, will discuss our R&D and pipeline progress. We will then open the call for questions. Joining the team for the Q&A portion of the call will be Xiaobin Wu, president and chief operating officer, Matt Chalas, our General Manager of North America, Mark Lanasa, Chief Medical Officer for Solid Tumors, and Ahmed Agarwal, Chief Medical Officer for Hematology. I'll now pass the call over to John. John?

Thank you, Dan, and welcome. I'm pleased to present our Q3 results today across every dimension of the business. V1 is executing at the very highest level in our history. The results speak for themselves. Financially, we continue to deliver rapid growth and strong earnings. Aaron will take you through that shortly. In hematology, Brukinza's powerful and sustained BTK inhibition continues to translate into clinical and real-world differentiation. Building on Brukinza, Bacalzi and Tachybrutidae are expanding our leadership and extending it well into the future. In solid tumors, We're living up to our promise that 2026 would be an inflection year. Last week, we shared data for three of our most promising programs at ESMO. We have now shared differentiated data for five pivotal late-stage solid tumor programs. We've reached a level of productivity that I think is very rare in our industry. And the model we have worked so hard to build is already delivering very tangible results and we've only just begun to scratch the surface of what's possible. Here we see Rukinza's performance for the quarter. Sales totaled $1.4 billion, growing 34% year over year, with U.S. sales exceeding $1 billion for the quarter for the first time. The underlying fundamentals continue to be very strong. Rukinza's not just a leader in CLL. It's a powerful treatment option across four other B-cell malignancies. And we are far from done. Brekenza, both as a single agent and in combination, continues to generate the most Phase III data across the BTKI class. We often talk about Brekenza's clinical differentiation. It was designed for complete and sustained BTK inhibition, and it remains the only CLL therapy to show PFS superiority over a Grutinib in a head-to-head trial. The results we see in the clinical trial data for Grutinza are increasingly reinforced in the real world, and the picture is remarkably consistent. This slide brings together six independent datasets in CLL, representing tens of thousands of patients across three endpoints, overall survival, Time to discontinuation and time to next treatment. Across all of it, the answer is the same.

All 21 hazard ratios favor Rukinza.

In overall survival versus Acala, the four large U.S. claims data sets, including Medicare, range from 16 to 25 percent lower risk of death. Versus Abrutinib, the reduction was 27 to 36. Taken together across U.S. and European patients, claims and health records, survival and treatment durability, and versus both Acala and Abrutinib, the real-world evidence consistently favors Brukinza. Brukinza has established a strong foundation in hematology, but it's only the beginning of what we believe our heme franchise can achieve. With Brukinza, Bacalvi, and Takadeg, we're the only company with potentially best-in-class medicines across the three key mechanisms of action in B-cell malignancies. So whether a patient wants continuous or fixed-duration therapy or requires an option after progression, we will be able to meet the need with the right medicine alone or in combination. No other company is positioned to do that. This isn't hypothetical. In the pivotal trials for the regimens on this slide, they're already reading out. And the data will be coming fast and furious over the next three years. And behind these three promising medicines, the next wave of heme assets from our prolific discovery engine is entering the clinic. And this includes small molecules, multi-specific antibodies, and novel cell therapies.

Now turning to solid tumors.

Over the past several months, we've shared differentiated data for five programs. Our GPC3-4-1-BV bispecific antibodies, our brain-penetrate PRMT5 inhibitor, our CEA-ADC, our CDK4 inhibitor, and our B7H4-ADC. Most companies have just one exciting asset. Some have two. From just the first wave of our solid tumor pipeline, we have five, all advancing towards registration-enabling development in roughly the same time. These programs target some of the most common and deadly cancers in the world, including lung, breast, liver, gastric, and ovarian cancer. Together, they affect millions of patients every year and account for millions of cancer deaths worldwide. When we started this company 16 years ago, the goal was simple. To fight cancer and to fight for life. And also to dramatically change how things were done in our industry by building a company that could sustain that purpose. And today that's no longer a vision. It's a reality. So how are we doing this? This slide reiterates something fundamentally different about B1. For years, we've talked about our goal to build a lasting oncology company, one that generates higher returns for each dollar of R&D investment by leveraging our global development superhighway. Today, we're seeing the results. Over the last three years, we've brought more new oncology medicines into the clinic than any other company in our industry. We are moving them through the clinic with exceptional speed Behind the power of our global development superhighway, our CDK4 inhibitor and B7H4 ADC programs show what this looks like in practice. Both moved from first in human to pivotal development in just two and a half years, allowing us to rapidly close the gap with the competition. And now we're seeing that pipeline advance into registrational trials, which puts D1 in an exceptionally select group So, if you look back at any 18-month period in oncology since 2010, very few companies have ever seen this level of late-stage productivity. Our peers on this list are the largest, most accomplished pharma companies in the world, with R&D budgets many times ours. And yet, there we are, among the top. Our scientists are generating more high-quality shots on goal. We're advancing them faster, and importantly, we're converting them into late-stage programs. And really, we're just getting started. At B1, we believe we've created something truly special. So, I just want to thank the team again for doing this. After these years of sustained investment and hard work, we've certainly built a model that's unique in the industry and is extremely difficult to replicate. It's built on four competitive advantages, rigorous and prolific internal research, our global development superhighway, global commercial presence, and an entrepreneurial culture driven by a deep sense of urgency because cancer patients just can't wait. These advantages create a self-reinforcing feedback loop. Together, they enable us to drive industry-leading R&D returns at scale, turn that innovation into profitable growth, and to fund a growing level of investment in next-generation medicines. Each turn of the cycle strengthens the next. That compounding effect is V1's greatest long-term competitive advantage, and the best way to maximize long-term value is to keep investing behind it. As Aaron will discuss later, we think it's important to retain the financial flexibility to fully fund the opportunities we see in the business. We believe this is the right approach to bring more transformative medicines to patients and to achieve our goal of building the world's leading oncology company. With that, I'll turn it over to Aaron to discuss our financial performance.

Aaron. Thanks, John. Our third quarter results demonstrate continued strong execution across the business with broad-based revenue growth, expanding operating income, and strong cash generation. Starting with our commercial performance, we delivered another strong quarter across the portfolio with product revenue growing 33% year-over-year to approximately $1.9 billion. Rukinza global revenues reached approximately $1.4 billion. representing 34% to sustain global leadership and growth in all regions. U.S. briefings of sales exceeded $1 billion in the quarter, representing growth of 36%. Growth was driven by continued strong demand, with trends consistent with those that I discussed last quarter. These include sustained high level of new patient starts, meaningful growth from all approved indications, improved patient adherence, and duration of treatment compared to relevant historical benchmarks. U.S. Burkina sales did have an approximate $50 million tailwind due to order timing, inclusive of an extra shipping day in the quarter. Tevibra generated approximately $243 million, growing 28% year-over-year. We maintained our leadership position in China and saw launches in other markets increasingly contributing to growth. Since the August U.S. approval and launch of the Horizon Regiment, we have seen encouraging early prescriber reception, reflecting the strength of the triplets' differentiated profile and first-line HER2-positive GEN. Our Amgen in-license portfolio generated approximately $167 million, growing 26% year-over-year. Overall, we are pleased with the breadth of performance across the portfolio and the continued strength of the underlying commercial business. Let's turn to the geographic composition of our business. Growth remains broad-based across every region. The U.S. generated approximately $1 billion in product revenue and remains our largest market. Macaulay launched in the U.S. in the relapse refractory MCL, and we are excited for this innovative medicine to be available for patients in this setting. Given the size of the approved indication and the timing of launch, we do not expect Macaulay to be a meaningful revenue driver this year. China contributed approximately $527 million, growing 21% in its seasonally high third quarter. Growth was seen across our commercial portfolio, with continued market leadership for both Tavimbra and Burkinza, and large contributions from Bacalli and Zahira. Note that foreign exchange contributed 7% of reported growth, given year-over-year renuity strengthening. While our Amgen portfolio delivered 26% growth in Q3, We are beginning to see some impact from biosimilars for Xgeva that was highlighted earlier in the year. This competition, along with potential VBP inclusion risks for Xgeva and Kyprolis, will likely lead to revenue pressure for these brands beyond 2026. Europe generated approximately $234 million, growing 41% driven by demand growth for Burkinza and launch uptake for Tavimra. And our rest of world markets contributed approximately $80 million, representing 58% growth. Key markets such as Japan and Brazil are making contributions that are increasingly meaningful at the enterprise level. Turning to the GAAP P&L. Total revenue was $1.9 billion compared with $1.4 billion in the prior year. Gross margin was approximately 88%. This includes a non-cash intangible asset impairment charge of $22 million associated with the company's decision to revert promotional rights for Pavese. Operating expenses totaled approximately $1.25 billion, representing 19% growth as we continue to invest behind the advancement of our pipeline and commercial growth. Moving down the P&L, we continue to demonstrate substantial scalability in the model, with income from operations growing 157% to $419 million, Even as we continue an increased investment behind the tremendous opportunity of our late-stage pipeline. And finally, net income totaled $385 million. GAAP diluted earnings per ADS for $3.28, compared with $1.09 in the prior period. Now turning to our adjusted results with a full reconciliation provided in the appendix of our results presentation. Adjusted income from operations increased to $612 million, representing growth of more than 79%. Adjusted net income increased to $539 million, while adjusted diluted earnings per ADS increased to $4.59, compared with $2.65 a year ago. Cash generation continues to build momentum, with free cash flow of 34% from the prior year. and 474 fielders. Turning to our updated full-year outlook, given our performance through the third quarter and our expectations for the remainder of the year, we are raising and narrowing our 2026 guidance. We now expect total revenue of $6.9 to $7 billion, compared with our prior range of $6.6 to $6.8 billion. We continue to see a modest net pricing benefit in the U.S. for Purkinza for the balance of the year. Looking ahead to 2027, we expect relatively stable net pricing. Note that the increase in our Medicare Part D manufacturer liability will likely pivot the modest tailwind we've seen in 2026 to a flat to modest headwind next year. This is a statutory increase associated with our specified small manufacturer designation for Purkinza. Our gross margin outlook remains unchanged in the high 80% range. We now expect operating expenses of $4.9 to $5 billion, a narrowing of the prior range of $4.8 to $5 billion. We expect GAAP operating income of $1.2 billion to $1.3 billion, an increase of $200 million across the range. And finally, we expect non-GAAP operating income of $1.9 to $2 billion. also an increase of $200 million across the range. Moving to income taxes, I'd like to provide an update on the income tax valuation allowance that I spoke about earlier this year. As background, we have historically been in a valuation allowance whereby the accumulated deferred tax assets we have have a reserve against them. Given our recent history of earnings, we believe there will be sufficient positive evidence to recognize a portion of these assets. Thank you for joining us. We plan on providing additional commentary for this in our fourth quarter call. As we look beyond 2026, I'd like to make one broader point on the trajectory of operating margins. The business is performing really well, and our underlining earnings power has continued to increase as you see in our guidance updates over the course of the year. This profitability has translated into free cash flow and an increasingly strong balance sheet, which provides us with increased financial and strategic flexibility. Moving forward, we now have multiple differentiated assets advancing into digital development across some of oncology's largest indications. Given the quality of these opportunities and those that will come from the next wave of our model, as well as potential business development, we intend to continue investing with discipline to maximize our impact for patients and value for shareholders. As I said last quarter, we anticipate 2027 operating expenses growth to be at least consistent with where we have been over the past several years given the size of our pipeline opportunity. As a result, while we expect operating income to continue to grow meaningfully, the pace of margin expansion is likely to be modest as compared to 2025 and 2026 as we balance year-term margin percentage gains with investment in future growth. And with that, I'll turn the presentation over to Lai.

Thank you, Aaron. We continue to make strong progress across our pipeline this quarter in both hematology and the solid tumors. Today, I will highlight several important clinical and development updates, including the new solid tumor data we recently presented at ASMO. Let me start with a few highlights across the portfolio. Opal Kinzer. In Tumor Naive Mental Cell Lymphoma, we have completed submissions in the US, Europe, and China, and the FDA has granted priority review. The mangrove results will also be featured in a plenary presentation at ASH. For Picausi, SLESHER 304 remains on track to complete enrollment before year-end. For TechDeck, the Phase II portion of Cadence 101 met its prime endpoint and the following discussion with the FDA. We are planning for a potential submission in mid-2027. I will come back to TechDeck in more details shortly. In solid tumors, we continue to accelerate our late-stage programs. For our CDK4 inhibitor, we are increasing the sample size of the Phase III Candela-302 study. Importantly, we are doing this to bring the study readout earlier. We have achieved first subject enrolled for our BSMH4-ADC StarStorm301 Phase III study. This marks the second start of a Phase III study in our solid tumor franchise this year. We are also advancing our GPC341BB bispecific into pivotal development while development of our PMT5 inhibitor, the CA-ADC, continues to advance following the data presented at ASIMO. Stepping back, This progress reflects our deliberate R&D strategy. We are building depth in disease areas where we believe we can establish leadership rather than developing individual assets in isolation. And we do this across small molecules, degraders, ADCs, and multispecifics, matching modality to biology, and increasingly building combinations from within our portfolio. Our goal is not simply to generate more molecules. It is to create the next treatment paradigm that can meaningfully improve outcomes for patients. Now let me come back to PECDEC. The Phase II study in relapsed refractory CRL achieved its primary OR endpoints with encouraging duration of response, PFS, and safety. were targeting a potential FDA submission in mid-2027. Our growing confidence in Cadence 304 is also allowing us to optimize the broader development program, where increasing enrollment number in 304 study from 500 to 600 patients to accelerate the readout, while remaining on track to complete enrollment in early 2027. Given our increased confidence in 304 outcome, we are converting Cadence 302 to a Phase II study. And importantly, we continue to expand the program. Our Phase III study of TechDeck plus StrongRow in relation to factory CRL is on track to begin enrollment in the first half of 2027. The right-hand panel highlights what we believe differentiates TechDeck Excellent Selectivity in Kynome and Protein Degradation Assays. Primarily a BTK degrader, TECDEC also provides a distinct secondary BTK inhibitory function that may increase the barrier to resistance and potentially extend the response duration. We will share additional data at ASH. Turning to solid tumors, I will start with our GPC341BP bispecific. HCC remains an area of significant un-mathematical need. In the U.S., liver cancer ranks the sixth in cancer mortality. Its incidence is similar to that of multiple myeloma and triple neck breast cancer and higher than that of the small cell lung cancer and the EGFR mutant non-small cell lung cancer. Despite this burden, there have been only two global phase III HCC studies since 2021. Far fewer than any of the other tumor types shown in this slide. At asthma, B2033 monocytopenia demonstrated a 36% confirmed response rate in heavily pre-treated second-line plus HTC with strong durability and a favorable safety profile without CLS. This compares favorably with historical TKI response rate of approximately 5-10% in this study. We are moving quickly into restoration or development. The potential pivotal third-line-plus cohort for China and Korea is fully enrolled. Before year-end, we expect to initiate both a second-line-plus single-arm study supporting a potential U.S. auxiliary approval pathway and a second-line-plus phase III confirmatory trial. were also very encouraged by the progress of our first-line combination with Tavembra and Avastin, supporting our plan to initiate a global phase III study in first-line STC in the first half of 2027. Let me first highlight the differentiated safety profile. The treatment-related adverse events shown here are predominantly low-grade, with very few grade III or higher events among the most frequently reported adverse events. Importantly, we have not observed CRS. Now turn to efficacy. In addition to the high response rate, I really want to emphasize the durability of the responses. Among the 27 confirmed responders, the six-month duration response rate was approximately 79%. The long-lasting responses we are seeing are reminiscent of the durability that has been a hallmark of immune therapies. Our second major asthma dataset was BGV58067, our brain penetrant PRMG-finding hedge. We have observed objective responses across multiple M-type deficient tumor types. In periods they treated M-type deficient EGFRY-type non-small cell lung cancer, the confirmed response rate was 38.5%, with median PFS of 8.1 months. We also observed intracranial responses in patients with brain metastasis. The potential opportunity extends beyond non-small cell lung cancer. MCAPS deletion occurs across a number of tumor types, and our development strategy includes pancreatic cancer, GBM, and potentially other tumors. In non-small cell cancer, we are already evaluating combination with PD-1 and chemo-CLP in first-line study. And in pancreatic cancer, we plan to begin evaluating combinations with the RAS inhibitors from our Revolution Medicine collaboration before year-end. Here again, our strategy is to take an encouraging early signal and rapidly build a broader development program around the differentiated properties of the molecule. Looking more closely at the efficacy, I first want to highlight the durability we are seeing. Responses have been durable, and we are also seeing patients with prolonged stable disease. This is encouraging because the benefit appears to extend beyond patients who achieve an objective response. Then another important feature of 58067 is brain penetrance. Among non-small cell lung cancer patients with active brain metastasis, the confirmed intracranial response rate was 30.8%. What I found particularly interesting is the low intracranial progression rate of 16%. This is substantially lower than what has been reported for DACO-DXD and docetaxel. And it is more in the range of what we see with CNS-penetrant target therapies, such as osimertinib. Let me turn next to BG-C477, our CEADC. At ASMO, we presented initial proof-of-concept data in heavily pre-treated CEA non-small cell lung cancer. The confirmed response rate was 60%, with a six-month DOR rate of 73% in Phase Ia datasets. We also observed a favorable safety profile, including nerve ratio or higher ILD or ocular events in the datasets presented. Approximately one-third non-small cell lung cancer tumors are estimated to have high CA expression. Based on these early results, we are developing C477 across the non-small cell lung cancer treatment spectrum. A global phage study in second-line non-small cell lung cancer is in planning. A first-line combination cohort with PD-1 is ongoing. We are also evaluating opportunity in earlier stage disease. Looking more closely at the efficacy, we are seeing broad activity across both squamous and non-squamous non-small cell lung cancer and cross EGFR centers. Within the non-squamous disease, the response rate was numerically higher in EGFRY type than in EGFR mutant patients. We are also encouraged by the durability. The six-month PFS rate was 76.2%, and the median PFS has not being reached as a data cutoff. Now let's turn to ASH. We have 45 accepted ASH drugs and the five oral presentations across Burkinsa, Dicauzy, and the Tech Deck, including Mangrove in treatment-naive mental cell lymphoma as the ASH plenary. We believe Mangrove supports the potential for Burkinsa to establish new chemo-free standard of care in treatment-naive mental cell lymphoma. MCLL, our seven-year-old survival data show life expectancy matching the general population, moving us closer to our cure zone ambition. And as John discussed, real-world evidence continues to report a survival advantage for Burkina Faso. For Pekosi, the frontline combination with Burkina Faso showed 100% three-year PFS rate, while the ramp-up data highlight convenience advantages over the next class. And for TechDeck, long-term clinical follow-up and the differentiated mechanism data continues to support its potential as the first and the best in class BDT category, including a distinctive design that may address resistance researchers. and the high selectivity among BTK degraders in the clinical relevant for blood assays. We'll have much more to discuss at our ASH investor event on December 14. Let me close with this overview of our upcoming milestones. As you can see, we have already addressed the vast majority of this today, reflecting the significant momentum across both hematology and the solid tumor portfolios. will provide additional updates on our 2027 milestones at J.P. Morgan. And with that, I will turn it back to John.

Thanks, Lai. We will now open the call to Q&A. Please limit the number of questions that you have so we can ensure that we have time to hear from as many attendees as possible. Operator, please go ahead.

If you would like to ask a question, please use the raised hand icon which can be found at the bottom of the webinar application. When you're called upon, please unmute your line and ask your question. We will now take a minute for the queue to assemble. Okay, we have our first question from Jessica Pye from JPMorgan. If you would like to unmute yourself, please, Jessica.

Hey, good morning, guys. Thanks for taking my question. A couple on the pipeline. Can you just expand a little bit on what's behind the time and shift on the filing for tachyperthic, for hereditary CLL? And then for the GPC3-4MDD bispecific, I guess for Mark or Lai, I think BioNTech had some interesting liver cancer data for their PD-1 VEGF bispecific combined with the B7H3 ADC in liver cancer. Can you talk about where you think your GPC3-4MDD bispecific might have advantages over that regimen? Thank you.

Thanks, Jessica. I hope you're well. I guess we can start with Annette and then move to Mark.

Thank you, John. Yeah, let me provide a little bit of color on the TACADEC update. So, first off, we're pleased to report the positive readout of the Phase 2 trial. As I mentioned in his prepared remarks, the study met its primary endpoint of ORR. And in terms of other endpoints, like duration of response, protection-free survival, and safety, The data is very strong and reinforces our confidence in the program. We did recently have discussions with the FDA on our potential X-related approval submission. And based on those discussions, the FDA requested some additional follow-up. And as a result of this, we are now planning to file for X-related approval in mid-2027. What I'll say is this is not an unusual request from the FDA, especially for a first approval of a new molecular entity. And so, again, overall, we remain confident in the program. And as Lai also provided an update, what we're doing for this ARS-204 trial, which is our head-to-head trial versus per the group NIP, we are increasing the size of that trial. And we think this will accelerate the timing of that interim readout and allow us to keep the enrollment timelines match. So, really looking forward to all of these updates in 2027. With that, I'll turn it over to Mark.

Thank you, Mitt, and thanks, Jess, for the question. We are very excited about the potential of our GPC3x41BP targeting bispecific and have increasing confidence that this will be a transformative molecule for patients with hepatocellular carcinoma. As you heard from Lai, at ESMO we recently reported a monotherapy response rate and later lined extensively pretreated patients of 36%. These responses were durable with a six-month duration of response rate of 79%. Now, critically, we're delivering that efficacy with a highly favorable safety profile. Now, hepatocellular carcinoma is somewhat unique among solid tubers in that cytotoxic chemotherapy is really not a part of the standard of care, and that's because these patients have compromised liver function and associated comorbidities. Therefore, while ADCs do have a meaningful response rate in this patient population, Tolerability is a major challenge, and therefore durability becomes difficult. With our favorable safety profile and very favorable efficacy profile, we have already been combining, as you heard from Lai, with Tavembra plus Fefacizumab in a frontline patient population. We've enrolled over 70 patients, so we think that we have clear line of sight, not only in the later line patient segment where we've shared Compelling Data, but also in earlier lines of therapy where our favorable safety profile will enable higher order combinations to maximize patient benefit.

Thank you, Mark. Next question, please.

Okay, we have our next question from Yigal Nacho Moxbit, and they're from City Group. You can ask your question, please.

Hi, I hope you can hear me. Thanks for taking the questions on the strong quarter. I just had three quick ones. Johnny mentioned, of course, the Fast and Furious data coming for the next three years for the CLL franchise. I'm wondering if at this point you're able to provide a little bit more granular timing with respect to the first PFS readouts for the fixed duration studies are the two that you're running, AV versus AV and versus DO. Second, maybe for Lai or Mark, with regard to the PRMT5 and the RevMed combination, do you expect or not expect to see a DDI with Rosant as, of course, we've seen with some competing PRMT5s? And third, on the CEA, anything to read into with respect to the differential efficacy on the mutants versus the wild types? Thank you.

Yeah, I think maybe we can start with Lai, and Lai, if you want to pass off to your team, please go ahead.

Happy to. I will just comment on the DEI question related to PMC-5 with the round mat assets. We have done preclinical modeling and so far data suggests there is no significant concern around the potential DDI. Certainly, this needs to be validated in the clinical setting. Maybe I'll pass this on to Mark to comment on the CEA ADC.

Thank you, Larry. Thank you, Yitao. Yes, so this is something that we noted in the early emerging data. However, I would caution that the number of patients included, particularly in the EGFR mutant analysis, is relatively small. We are very excited about what we're seeing in terms of the response rate across all patients with non-small cell lung cancer. And importantly, durability is strong across these patients as well. So we are currently in our dose optimization and expansion phase, and we'll be able to share larger data sets in the near future. Amit, can you comment? Yeah.

Thank you for the question, Iqal. So on the two Phase III studies, the Celestial 301 study where we're comparing CS to VO and the Celestial 304 study where we're comparing CS to AV, again, as you know, both of those are event-based endpoints, and so we haven't shared yet the approximate timelines, but we're hoping to do that in 2027. Overall, I would say things are going really well with the CS program. We will have updates at ASH from the 101 study, so we'll share some updates in 2017. Thank you so much. Thank you very much.

Next question, please.

Okay, our next question comes from Sean Laman from Morgan Stanley.

Good morning John and team. Congratulations on the results and hope everyone's well. I have two questions. So the first one relates to the RevMed collaboration. So you're funding and conducting the Phase 3 Resonate 312 CRC study. What does that responsibility indicate about your long-term ambitions in precision oncology is the first question. The second one, maybe one for Aaron, is just the commentary on margins. So I think you said expect a more moderate pace in margin expansion versus this year and last year, but are you expecting margin to keep increasing from here given the significant R&D investment B1 has going on? Thank you.

Sure, I think we'll start with Lai and then move over to Aaron. Thank you.

Thank you so much for the question. This is the major reason I think the RENMED wants to do this collaboration with B1, because they believe in our development superhighway. So we're conducting the C1-2 study, which is the frontline study in the CRC, which is testing the direct song in combination with the standard care. We are very excited about this opportunity and hopefully this will help runmats to really fulfill their ambition about being the leader in the RAS space. And certainly this will also give us opportunity to potentially combine our pipeline sets with Even further, as I think we mentioned in the press release, in addition to combining the PMT-5 with the RENMED assets, we're also combining our EGFR METS tri-specific with RENMED assets. As you can imagine, a combination with Zodon in the CRC will be one of the leading indications for us to explore.

And thanks for the question, Sean. So first, let me just start by saying, you know, we are in an incredibly strong position financially, and we're really proud of what we've accomplished in our profile. The business is performing really well, and the setup continues to support growth, albeit at a larger base of business as we look forward. Since 2024, we've shifted, as you know, to a profit-making business with operating margins that are set to expand by more than 10% in 2026. based on the midpoint of our current guidance. That's something we're really proud of, and candidly, as you see in our guidance updates this year, it's at a pace ahead of where we thought we'd be at this time. Moving forward, our key message is that we're building a company to last and is supported by increasing financial flexibility. We have tremendous opportunity with our pipeline and our repeatable innovation model, and we're going to invest to realize that full potential. As a result, we anticipate operating expenses to grow at a similar rate, as I said last quarter, to what we've seen over the last couple of years. And taken together, we do expect we will be able to fund our future ambitions while driving meaningful growth in profits, although the pace of growth in profit margin percentage will be modest as compared to what you've seen in recent years. Thanks for the question. Really appreciate it.

Thank you.

Our next question is... Our next question comes from Andrew Behrens from Leerink. If you'd like to ask your question, please.

Hi, thanks and congrats on all the progress, guys. Definitely pipeline's expanding very rapidly. I guess two for me. One, as we go into ASH, How do you think your collaboration with RevMed positions this program relative to companies that have a head start in combos like Tango and PDAC and then Bristol and Lung?

Yeah, thanks for the question. Why don't we start with Anit and then move to Mark? Yeah, thank you for that question.

So in terms of the DACA-LINK program, I think, again, we're very excited about the program as a whole and what we're presenting at ASH. Lai alluded to this a little bit. I think one of the interesting sort of preclinical presentations that we will have at ASH is really sort of this idea of having a secondary inhibitor function and really what we think this is going to or how we think this is going to translate into the clinic is particularly on the durability side of things. Beyond this, I think we're very well positioned to execute on that broad development plan for TACADEC. You heard a little bit of an update on our headrest study versus PURTO, which is designed to show that TACADEC is clearly superior to PURTO and so as PURTO moves in earlier lines, I think having this particular data set is going to be particularly important. But beyond this, we're also initiating a study of Tachytec for Sondro in the relapse CLM space, which we believe will be the best fixation treatment for that patient group, regardless of what type of treatments that they've received in the frontline treatment program. And beyond this, we also see major challenges with the triplet regimen that PERTO has just released on the PERTO and Rituximab dataset, because the CV20 antibody really might be adding more toxicity there than providing clinical benefits. And so overall, we're very confident in the program and really looking forward to some of these new studies with Agavec. Thank you.

Now, maybe we take over to Mark.

Thank you, Amit, and thank you, Andy, for the question. We're very excited about the opportunity to combine our CFS penetrant PRMT5 inhibitor with the RevMed RAS on molecules. In addition to the clinical data that has been disclosed for that combination, we also have strongly supportive preclinical evidence that we've generated in-house for that combination. And I would highlight that in the recent disclosure that we had at ESMO, there were really a large number of patients treated across a broad number of solid tumors. So we have a substantial global footprint in our Phase I study. The amendment for the RegMed molecules has already gone through. It's posted on clinicaltrials.gov. We anticipate that enrollments will begin imminently. There's very high investigator enthusiasm. Therefore, we believe that our development superhighway, again, can close any time gap. And as you heard from Lai, we're also not expecting a drug-drug interaction. Therefore, we think that we have all the ingredients in place with a best-in-class PRMT5 inhibitor plus a development superhighway that we can meaningfully close the gap and ultimately be leaders in this space.

Thank you. Okay, our next question comes from Gregory Render from Truist Securities. Gregory, just checking if you can hear us. If not, we will move on to the next question.

Yes, I can. Thank you. Good morning, Jonathan. Let me add my congratulations on the progress and the results. Maybe just a question to follow up on the tacky bag updates. I get to see your increased confidence, but maybe just to talk a little bit about just confirming your confidence about accelerated approval filing once you implement the changes that you're highlighting today. Maybe just talk a little bit about how you see You know, that peak opportunity perhaps evolving, do the updates in that confidence perhaps help to alter or maybe inform the longer-term positioning? And just lastly, if I may, I'm just seeing the mention of the CSU trial and just broadening in the INI, maybe talk a little bit about that potential expansion and how intact that is. Thanks so much.

Thanks for the question. It's always hard to Thank you, John, and thank you for this question, Greg.

So what I would say is, again, I think right now we're very happy with the results we've seen from the phase two trial, and particularly when it comes to explicit approvals, you know, we certainly want to make sure that we respect that regulatory process, and so without getting too ahead of ourselves, we remain confident in what the data set shows and the unmet need in that particular case. and I look forward to continuing their engagement with the FDA. Now, ultimately, I think the accelerated approval opportunity is still a smaller opportunity in the broader context of the program and particularly the trials that we're outlining now, whether it's the head-to-head versus per the group name or even the combination trials and then future development that we have planned for TACADEC as a whole. We think that those are more meaningful opportunities, and certainly as that head-to-head study reads out, it will open up the possibilities for a broader group of CLL patients to benefit from TACADEC. And so we certainly think that the opportunity is much more beyond the accelerated approval opportunity. And perhaps I'll ask Lai to comment on the CSU part of things.

Yeah, we took a little bit of time to really contemplate our strategies for our BDK-CDAC. We do believe with this extremely long half-life, we have a potential advantage for this molecule. We are on path to initiate the CSGO trial early 2027.

All right, thanks. Next question, please.

Our next question comes from Kalpit Patel from Wolf Research.

Hi, this is Nikki Allen for Kalpit. Thank you for taking our question, and congrats on the results. On the last half on the 1L breast cancer study, we noticed that the trial increased in size. Given that this is an event-driven study, can you help us understand how adding more patients gets due to the readout sooner, or do you think the required number of events change, or are some of the same statistical assumptions? Thank you.

Thanks. I'll pass that to Mark.

Great. Thank you for the question. So, the Candela 302 study is progressing very well. We're actually recruiting slightly ahead of our internal projections, and we've had very strong investigator feedback to date on the study design and the early experiences in the trial. Now, in that context, Upsizing the study has a number of statistical benefits that are conveyed by increasing the power of the study, and it is our belief that we will be able to enroll this somewhat larger study, approximately 10% larger study, in the same period of time we were originally projecting for the originally sized study of a little over 1,000 patients, now 1,200 patients. without changing the assumptions in terms of the overall event rates, that actually pulls in our timeline somewhat because we have increased our statistical power. So again, if the period of enrollment is fixed, then we will get to that readout earlier.

Thanks, Mark. Next question.

We have our next question from Yaron Werber. He was from TD Cohen.

Great. Thanks so much. Congrats on all the progress. So, maybe just two quick questions. So, first of all, on PECA Brutideg, the push-up sort of submit next year, does that have to do with looking at more durability data? And are you thinking about filing for a broad label, essentially including both PTC inhibitors, covalent, non-covalent, and a BCL2? And then secondly, for the RASMQ frontline CRC study, I just wanted to catch, in combination with chemo, is that phase three starting by year end this year or is it early next year? Thank you.

Thanks so much. Hope you're well. And I guess we're going back to the specific book.

Yeah. Thank you, John, and thank you for that question. So in terms of the population for the phase two study, Certainly, this was a mix of patients who had a covalent VTK inhibitor and a PCL2 inhibitor as well as patients who had a covalent, non-covalent, and VCL2 inhibitor. And we've seen encouraging results across those populations. To your question about the sort of shift there, it is related to the fallout that we see. And certainly, you know, this is something that we can, you know, expect given that new molecular entities, typically the FDA, can ask for more data in terms of both the safety as well as the durability data. And so that's where we are with that one. And then I think the other question was for Mark.

I can take the other question which is related to the SU12 study for RANMAT. We are initiating this study. We're working very closely with RANMAT. At this moment, we won't be able to comment on exactly the time of the first patient to be dosed.

Thanks so much. Next question, please.

Okay, we have our next question from Ziyi Shen, who is from Goldman Sachs.

Good morning. Thank you for taking my questions. Congrats on another feed and raise. First, it's going to be on Brutinsa. Brutinsa has been the BDK leader for years now, and we have not seen a slowing down in market share game trends. So what has been the drivers in the past few quarters behind the acceleration? And also under this context, how do you see the impact of the new hurdles updated data for the CIL 313 trial in the first line with a much longer median follow-up period. So that's my first question. And second, we are really a big fan of GP3-4MBB, excited about the data at small. Given the safety profile now looks very good, we're kind of curious about the plan for 4MBB-based pipeline expansion. What will be the next big thing, you know, coming from 4MBB-based by Pacific that we could be seeing and also Pru, the foreign VP based by specific design if expandable to broader pipeline. Thank you.

Sure. I think that we'll start with Matt, jump to Amit, and then go back to Lai because Mark may be getting tired today.

Thanks, John. Yeah, we're very pleased with the momentum in Verkenza. And in terms of drivers, we continue to be a new patient start share leader. across our indication settings. This is driven by very strong long-term data across CLL patient types and physician experience that's leading the preference. We've also, as you heard Aaron comment, have been very pleased to see our duration of therapy and a more mature view on that with claims of real-world evidence that's more mature and allowed us to get a good read on what we believe is a pretty substantial duration of therapy. And then we've also seen growth come from indications beyond CLL in our other B-cell malignancies, particularly with some strength involved in strength. Now, with regard to Pyrido, happy to comment on that as well. You know, we, of course, know this was studied in a limited patient population, has limited data in elderly patients, no long-term data. and really limited differentiation on safety, like infections, cytopenias and discontinuation rates. But I think the most important factor is that these resistance mechanisms to PIRTO confer resistance to covalent BTK inhibitors. As a result, physicians don't want to burn a line of therapy, and thus far we've really seen uptake contained to the later lines of therapy. But I'll hand it over to Amit to make some further commentary on that.

Yeah, thank you, Matt. I think in terms of review on the frontline setting, We continue to believe Rupinza is the gold standard when it comes to the data that's been presented so far. When you look at especially the long-term outcomes from the six-year PFS of 74% with the COVID adjustment of 77% and an overall survival of 84%, really I don't think the data stacks up for PERTO just yet. Obviously the approval for PERTO at the front line was based on the Bruin 313 study, where Berto was being compared to PR which was really in the U.S. as an obsolete control arm. And the initial results were presented with a very short follow-up. Now the biggest problem with this study besides the control arm is really the demographics view of that study. So the study enrolled really young patients and when you look at the safety data there it really needs to be evaluated in the light of that patient demographics. And as Matt alluded to this When you look at the Bruin 314 data, there's very little differentiation between Berto and Ibrutinib. On efficacy, there are two events that separate Berto and Ibrutinib. The last time this data was presented, so basically we're talking about 48 versus 50 PFS events. And on the safety side, Berto just did not show a significant difference versus Ibrutinib in terms of infections, cytopenias, and discontinuation rate. and even the AFIL breed, when you age match it, it really is very comparable to what we've seen in Sequoia. And in addition to this, as Matt highlighted, when we talk to thought leaders in CLL, the idea of effectively giving PERT to a head of a Covalent BTK Navigator and potentially burning a line of treatment, if you would, really is not appealing. And so we're not surprised that there is very limited uptake for PERT on the frontline. With that, I'll hand it to Mark.

Maybe I can jump to this question. This is a really very good question. I'd love to answer it. So I want to mention beside the greater safety profile, what we have observed with GPC-34, maybe this new kind of immediate MOA is really are validated by the clinical data. If you look at the spider plots, we actually have a patient who not only if the response is durable, we actually have some patients begin to show up the response very late. So there was one patient become a responder at week 36. You know, 4-on-BB isn't the strongest kind of the T cell activator. So when you combine this potentially in the first line with some other agent which can help to control disease, which we believe this drug perhaps will perform even better. So, over the years, we have built this really strong feedback loop between the preclinical to the clinical. So, once we, you know, our preclinical abscesses of bioGPCs to 4MVB was validated in the clinic setting, we began to really think about how can we maximize the value of our pro-patriot 4MVB platform. So we're working on two things. One is really leveraging this unique binder as well as the testing system to set up a whole set of the TA411BB pipelines. So I can assure you there are many programs we're working on at this moment. In addition to that, we're also working on next generation. We believe there is further room to improve on the current 411BB T-cell activator. So that is also coming. So starting from next year, you'll begin to see new molecules coming from our 4MVP platform. This will be one of the important technology platforms we will leverage to build our pipeline.

Next slide. Can we get another question, please?

Okay. Our next question comes from Michael Schmidt from Guggenheim. If you'd like to unmute yourself and ask your question, please.

Hey guys, thanks for taking my questions. I just had a housekeeping question on guidance. It looks like the updated guidance suggests flat to down revenue in the fourth quarter. The Penn Street is wondering if that is just seasonality, conservatism, or if there's anything else going on towards the end of the year. And then just regarding the mangrove, Fennery and Ash, just reminders of the opportunity in that particular setting for the group and the franchise. Thanks so much.

Sure. Thanks, Michael, for the question. We'll start with Aaron and then move on to Yvette.

Great. So thanks for the question. Obviously, we're very pleased with our performance through the first three quarters of the year. We're doing $5.1 billion of revenue, 33% growth. I mentioned when you account for the $50 million in timing that I noted, sequential and year-over-year growth are largely consistent where we've tracked through the first three-quarters of the year. Similarly, expenses reflect typical seasonality that you see in the industry as well as the increasing investments from our late-stage R&D programs. The guide, therefore, reflects a fairly consistent investment growth for those growth that you've seen over the past two years, and that will continue into 2027, as I said.

Yeah, thank you, Aaron. So, in terms of mangrove, again, I think, you know, this is really exciting in terms of just what this means for front-line MCL patients. As we've indicated before, mangrove is the first and only chemo-free regimen for these patients that has shown superiority over a chemo regimen. And the data and the fact that this has been accepted as a plenary presentation shows really speaks to the broader excitement that the oncology and hematology community are seeing with this particular regimen. And similarly, I think the priority review, we're hoping that this will come to the patients very soon. But I'll turn it over to Matt to talk a little bit about the commercial opportunity here.

Thanks, Amit. Just to put it into context, MAML sells about 4,000 U.S. patients a year as compared to right around 20,000 CLL patients a year. So that gives you a As you heard from Amit, there's a really important unmet need for effective treatment options in frontline mantle cells that are supported by robust clinical evidence, particularly in the setting where mangrove was studied. So this opportunity with a chemo-free option in previously untreated mantle cells with the strong efficacy and safety data that will be bringing to the market, we think, when approved, will lead to extending the overall BTK class share within the space. And then, of course, we believe that we'll take grand share within that class and really drive some growth here.

All right. Thank you.

We also submitted the application in Europe and China. This is also a first-line mental health patient in China. and Europe Brussels, 3,000 and 4,000 each. That provides additional opportunity for us.

Terrific.

All right.

Further questions? Are there further questions?

There are no further questions. I will now turn the call over to John Oyler for closing remarks. Thank you.

Thanks so much. In closing, we've never been better physicians. Our commercial business is delivering, our pipeline is deeper than ever, and our model is proving repeatable. The work ahead is significant, but so is the opportunity. I really want to thank the patients and the families that we serve, our physicians, our partners, and our more than 12,000 colleagues around the world whose focus and urgency make our progress possible. Thank you all so much for joining us today and have a wonderful week.