Great. Good afternoon, everyone. My name's Jessica Fye, a biotech analyst at JP Morgan, and we're continuing the 43rd Annual Healthcare Conference today with BeiGene. I'm going to pass it over to BeiGene's CEO for a presentation, and then we're going to follow that with some Q&A. If you're in the audience and you want to raise your hand, someone will bring you a mic, or you can submit questions to the iPad. But with that out of the way, I'd like to call up John Oyler, the company's co-founder and CEO.
Thank you.
Hello. Thank you. It's great to be here in San Francisco again as we enter our 15th year as a company. In this short time, we've emerged as a top oncology innovator, and we're now poised at a true inflection point for our next phase of global growth. Of course, you need to take a moment and review all of our disclosures. I hope you read fast. As an investor of ours recently mentioned to me, BeiGene reminded him a lot of Amazon, and there is some truth to our shared DNA. Much like Amazon, we made bold strategic investments to build important core differentiating capabilities with global scale for the future state of our industry and the world.
For years, many people have neither understood nor appreciated these investments, but today we've reached a true inflection point where the fruit of our investments is paying off and about to become very clear. So in a snapshot, after years of investing significant cash to build these strategic advantages, we're now an enterprise that is generating cash through our operations. We reported $1 billion in total revenue in the third quarter, and our BTK inhibitor, Brukinsa, is now the number one BTK in the United States in new patient starts in both the front line and the relapse refractory CLL indications and four other approved indications. Our team brought an industry-leading 13 potential new medicines into the clinic in 2024, which places us at the top of the industry in terms of the productivity of our R&D organization.
Lastly, we changed our ticker symbol to ONC, announcing our plans to rename to BeOne Medicines, and we're re-domiciling the company from Cayman to Switzerland, subject to shareholder approval. We also opened our flagship U.S. manufacturing facility in New Jersey. These strategic moves give us a strong foundation for future global growth. Our company was purpose-built from the beginning to address the long-lived challenges to return on investment in our industry. I think, as you know, it's not getting any easier to generate ROI on each R&D dollar. Clinical trials represent more than 75% of the total cost to bring an oncology medicine to a patient. These costs are rising with CRO-run trial costs per patient nearly tripling in recent years to $250,000-$300,000 per patient.
Regulatory policies such as Project Optimus are meaningfully delaying programs and increasing phase I trial costs due to increased patient requirements and time, and increased competition exists for nearly every validated target. Pricing reform also, for example, IRA, is placing direct and indirect pressure on innovators, but we built this company from inception for a world where we envision these challenges, and at our core, we have always strived to build an organization that has the capabilities to be more efficient both on cost and time. Most importantly, our internal clinical development team of 3,600 colleagues all across the globe allows us to develop medicines with much greater speed and at much lower cost than our industry peers. This is paired with our internal research and our internal manufacturing to enable a fast-to-POC approach that shaves meaningful time from early-stage development.
We're innovating with intentionality and building best-in-class combinations to win in the increasingly competitive commercial landscape. We're doing this by building sustainable franchises in large market opportunity areas such as hematology, lung, and breast cancer. This is very similar to what Gilead was able to do in HIV or Vertex and cystic fibrosis. 2024 was a remarkable year, even by our company's high standards. We eclipsed $1 billion in quarterly revenue for the first time in our history. The significant top-line growth, coupled with disciplined investment, led to positive cash flow from operations in Q3, another milestone in our path toward a self-sustaining business model. These results are just the tip of the iceberg as we're now at scale with a founder-led organization and an entrepreneurial culture and a deep sense of urgency, and we're poised for superior financial returns.
As impressive as these financial metrics are, our R&D performance surpassed even this by bringing 13 potential new medicines into the clinic in 2024. And it's not just numbers. These are some of the most compelling early programs in the entire industry. And this was achieved while building our own far more efficient, truly global, CRO-free clinical capabilities. This 3,600-person organization operates across 40 countries, with 50+ people in Brazil, 200+ in Australia, and of course, hundreds across the U.S. and Europe. Our focus for 2025 is to deliver on three strategic pillars. The first, we'll solidify and deepen our hematology leadership with Brukinsa and CLL and follow this with our two pivotal stage programs, Sonro, our BCL2, and our BTK-CDAC degrader, that both have the potential to be practice-changing. Secondly, we're advancing our pipeline of internally developed assets from this prolific R&D team, which you should pay attention to.
This includes some tremendously exciting programs with near-term inflection points. And thirdly, we're leveraging our strong top-line revenue growth and our disciplined investment to drive superior financial performance and create a positive feedback loop for future growth and value creation. So first, let's speak about our hematology franchise. We can't talk about it without starting with Brukinsa. It's really an incredible medicine. In under two years from its first approval in CLL, despite being the third entrant to the market, Brukinsa has now become the BTKI class leader in new patient starts in the U.S. in both front line and relapse refractory CLL, as well as all other indications. How did Brukinsa become number one? It wasn't luck. It wasn't chance. Brukinsa was designed to have 24/7 inhibition of BTK in all disease compartments. Ibrutinib is a great medicine, but it has known efficacy and tox challenges.
We designed Brukinsa to address those. Ibrutinib simply is unable to reach the PK it needs to sustainably inhibit new BTK that's generated during the course of the day. Acalabrutinib, the second approved BTK, was designed to be safer, not more efficacious, and as you can see here, again, it leaves a lot of room on the table, not able to inhibit BTK all day long, and lastly, you can see Brukinsa, complete, sustainable inhibition. Our hypothesis was proven correct by the ALPINE trial, where Brukinsa demonstrated sustained superior PFS efficacy and lower cardiac tox in a head-to-head study against ibrutinib in all comers. Brukinsa is the only BTK to prove superior efficacy to ibrutinib. We show here in the subset of deletion 17p p53 patients, which are the patients that are most likely to need medicine and progress.
We've shown this dataset head-to-head with ibrutinib because acalabrutinib also ran a head-to-head study in this population, and we can, with all the qualifications of cross-trial comparisons, see both here. Although imperfect, this is the best comparison as they both have ibrutinib as a control arm. Please note, across these studies, ibrutinib is relatively consistent across trials at 42 months, 32% or 36% remaining patients, milestone PFS. This same time period, Brukinsa is 59%, and acala has actually crossed over ibrutinib, and it's only 28%. That's actually 8% worse than ibrutinib, so yes, at the last data readout of this study, despite declaring a hazard ratio of one and non-inferiority, there was a decline, and I can't help myself from pointing out that since this was published, the treatment naive arm of this ELEVATE study was updated 4x . The relapse refractory has never been updated.
This is September 2020 data. And all this compelling data and our excellent commercial team have generated exponential growth in Brukinsa global sales. This is strengthened by the broadest label in the BTKI class and approvals in more than 70 markets around the world. Again, we're the only BTK with a superiority in its label. We're the only BTK with QD and BID options. We have the ability to do small dose adjustments, and we anticipate a new tablet formulation that will reduce pill numbers this year. So that sounds great. We talk about building a CLL franchise in a $12 billion space, and we really believe we can, as I mentioned, the way Gilead did in HIV. We can provide the best solution for patients. We can be insulated from pricing pressure and competition. So how do we do that? Well, investors have raised three concerns around this.
First of all, they're legitimate concerns, so we'd like to talk about them. The first is how fixed duration acalabrutinib plus venetoclax, the data that was just presented in AMPLIFY in December at ASH, could impact the BTKI market. The answer to this is simple. The AMPLIFY data was underwhelming. It showed surprisingly low MRD rate, failing to achieve a deep MRD response. The PFS was also disappointing and is likely to deteriorate further, although it's early. The short-term safety liabilities are real, and it's unclear if they outweigh the benefits of time-limited therapy. The second issue is whether pirtobrutinib is a threat to Brukinsa. The ASH PFS data that was presented for pirtobrutinib deteriorated from over 20 months, I think it was 22 to 14. So it's unlikely to be a threat to Brukinsa, and we actually are starting a head-to-head study against pirtobrutinib with our BTK CDAC degrader.
I think probably the right question is, is that a huge threat to Pirto? Lastly, the last point, which is a fair point, is around how do you maintain price in a world with IRA and with patent expiry? I think the underwhelming data from AV provides an incredibly low hurdle for us to jump over for a price premium. We're really confident that Brukinsa and our franchise, combinations with Sonro or the degrader, can far outperform this hurdle, even Brukinsa alone. We're going to share that data in the next few slides because it's so important. What do you need for a fixed duration therapy? It requires three things: a deep response that's measured by undetectable MRD. The precedent data for VO was 75%-85%. You also need impressive and sustained PFS. You need to be comparable to continuous treatment.
And third, you need safety during the treatment period, this first 60 weeks, that adds only a minimal liability over a continuous therapy like Brukinsa. And remember, there's very few long-term safety issues with a continuous Brukinsa. So you can't have much of an additional safety burden if you want to have a fixed dose combination therapy. So let's see how the data actually looks. The first point I'd make is AMPLIFY did not show a deep MRD response. As I mentioned, the precedent MRD for patients that are fit with VO was 81% to 85%. AMPLIFY showed an MRD level for VO, for I'm sorry, for AV of 34%, 34. Actually, AV was noticeably worse than chemo. And AVO was worse than VO. Just for a reference, Brukinsa plus Sonro is 91% in an all-comers population. This is what we're looking for in a deep response.
Secondly, AMPLIFY did not show comparable PFS. Zanu's 36-month PFS is 84%, 83% at 42 months, and over 75% at 60 months. Precedent VO is similar to Brukinsa at 36 months, but it deteriorates noticeably over time. AV was notably worse than Brukinsa, VO, and VI at 76.5% at 36 months, and very noticeably, and you'll see the curve on the next page, potentially deteriorating thereafter. Clearly, more follow-up is needed, and AVO, again, in this setting, is numerically worse than VO in a similar population, so let's see the actual data from the PFS curves. Here it is. Note the 84% for Brukinsa, and at AV in the same time period, 76.5%, and note just after this data cutoff, the 36-month milestone, the shape of the curve with AV. This level of progression begs the question, is this a fixed duration therapy, or is it an intermittent treatment?
AMPLIFY also showed a challenging safety profile during the treatment period. This slide is going to compare safety over the first 60 weeks of treatment to assess any additional tox created by combination. As you can see, in all greater than three-grade TEAEs, the infection rate and the treatment emerging events leading to death and discontinuation, there's a substantial additional toxicity burden put on these elderly patients during the first 60 weeks. For AV, this is serious. For AVO, I think it's quite serious, and the fundamental question here is, is the juice worth the squeeze? In this case, the juice is highly dubious, but the squeeze comes at a substantial cost, so fixed duration has issues, it's true, but the good news is we believe the combination of Brukinsa and Sonro are going to address these.
This is going to become the preferred fixed duration regimen of the future in first-line CLL. Our data speaks for itself. 91% MRD, flatline PFS curve. I know you see this a lot of times, and it's in 20 patients, and it's with a few months follow-up. That's not the case here. There's a lot of patients, and there's substantial follow-up. This is a real curve. Our phase III pivotal sonrotoclax trials nearing enrollment completion against actually what's a relevant and widely used comparator, VO. We've also had phase II studies in early registrational potential in CLL, Waldenström, and MCL, and we're planning to initiate two additional phase III trials in CLL and MCL in the first half of 2025. And we also think Sonro may be able to be used outside of CLL and B-cell malignancies in multiple myeloma. The second point was around pirtobrutinib.
I'm taking a moment to just go through the degrader because we're a major player in degraders, and we really believe in this, and we think the mechanism's not well understood. Everyone understands the third piece of this, which is around scaffold function. You remove the signaling from the scaffold function. That's true. But the first piece is degraders are catalytic. One degrader molecule can degrade multiple, multiple, multiple proteins. So you have a catalytic action. You don't have this with inhibitors. Secondly, degraders have a higher barrier to resistance because they retain activity even in the presence of mutations that would otherwise abrogate the binding of a small molecule inhibitor. And we have seen this preclinically, and it appears we're seeing this now clinically. So we're huge believers in this in the BTK space, but we think it bodes well for patients all across all sorts of indications.
So we believe degradation is a big deal. How do we compare? This is how we compare. This is our CDAC program that's enrolled over 400 patients. It's the most advanced in the clinic. It's shown striking early efficacy and safety data in heavily pretreated population. We have an ongoing phase II expansion in relapse refractory CLL that's potential registration enabling and aggressive development plans for earlier line of therapy. This includes a head-to-head trial in second line against Pirto. Side by side, you can see the recently reported Pirto data with a deterioration from over 20 months to 14 months, and we're really excited about this program. So if you look at our portfolio against our competitors, you can see we're a leader in the wholly owned potential best-in-class molecules in CLL across multiple therapeutic modalities.
We believe these combinations position us to change the standard of care dramatically across all lines in CLL. And with the underwhelming AMPLIFY and Pirto data, we're well positioned to build on this strong franchise in the $12 billion CLL market, and we will be protected from pricing pressure from these competitor medicines. We're truly poised to be a leader in heme. We've established the foundation in CLL. We're growing our leadership, and we're expanding our indications, and soon we'll be maximizing our impact. So secondly, I'd like to talk about our prolific R&D early pipeline. As you can see on this slide, we've never been so active, and it represents rapid growth driven by this incredible internal R&D team. While we're advancing our leadership in hematology, we're building a deep and innovative pipeline to match. We've chosen six of these programs to quickly highlight.
They're all extremely promising and have huge market potential. POC data in the next 6 to 18 months. You really should pay attention to each of these. Relative to our peers, we're now one of the most prolific R&D companies, 13 potential new medicines brought to the clinic in 2024, and despite being almost entirely oncology-focused, and oncology trials are far more expensive than other indications, we actually have a cost advantage per trial shown here on the right, and the time and cost advantage capabilities we've built enable us to operate faster and at a lower cost, allowing us the flexibility to reinvest in research at a higher ROI. When I say faster and lower cost, what do I mean? As you can see, we're outperforming the industry benchmarks from preclinical through dose escalation as part of our fast to POC strategy.
On the preclinical side, we've shown we can advance our medicines from GLP tox to the first subject enrolled in less than 10 months. That's 30% faster than the benchmark. We're also rapidly enrolling our dose escalation and dose expansion cohorts. Using CDK4 as an example, we're able to enroll those dose expansion cohorts in just 6.4 weeks, 3x faster than the industry, which enables us to catch up with our competitors, and we've enrolled 125+ patients to date. The same is true for the BTK-CDAC degrader, where our enrollment speed and dose escalation and operational excellence has made us the leader in this space with 400+ patients enrolled to date. Taken together, we're operating at a much greater speed that translates clearly into greater cost efficiencies.
This becomes more important when you consider the competitive landscape of these programs, of which many of our pipeline assets have the potential to be first-in-class or best-in-class. So these advantages have allowed us to advance one of the most exciting pipelines in the industry. This slide highlights some of the hallmark programs, many of which we believe are compelling. We're approaching proof of concept for all of these programs in the next six to 18 months, and we have more information on the programs in the following slides. I can't do them justice, so I encourage you to review them after the presentation. Despite CDK4/6 inhibitor success, there's unmet medical need because all of these have been associated with dose-limiting tox and development of resistant mutations. Our potential best-in-class CDK4 spares CDK6 mediated and off-target toxicities. There's over 130 patients enrolled on this study.
The clinical investigation has revealed how low rates of heme tox exist, encouraging PD data as well as preliminary clinical efficacy. Additional study updates will be reported at future medical conferences this year, and POC is expected in the first half of 2025. Planning is underway for phase III studies in first-line and second-line HR-positive breast cancer. The second program we'll point out is our pan-KRAS. KRAS mutations are present in 19% of cancers. There's first-generation KRAS inhibitors that are mutation-specific and may be limited in their utility. They also may have dose-limited RAS pan-RAS inhibitors because they don't spare KRAS, HRAS, and NRAS. Our pan-KRAS will test the hypothesis that hitting this harder with a better window can have superior efficacy. The next program we've listed here is our B7-H4 ADC. This is an exciting validated target, and we actually think we have the potential to be first-in-class here.
This is expressed in multiple solid tumor types, and we're planning development in breast and gynecological tumors. We have over 50 patients enrolled, and again, first data disclosure second half of this year. Our EGFR CDAC, we love CDACs. We love degraders, if you haven't noticed, and this is an exciting target, and we should have POC data the second half of this year. This is the fifth listed, it's really a twofer. We're after MTAP deletion that's found in 15% of all tumor types, and we have a second-generation MTA cooperative PRMT5 that selectively kills MTAP deletion tumor cells and spares normal hematological cells. It has superior preclinical potency compared to first-generation inhibitors, but we're combining it with a MAT2A that's also in the clinic, and we believe this combination has distinct complementary synergistic mechanisms preclinically and hopefully clinically for increased tumor killing. Combination POC is expected next year.
Lastly, we have our IRAK4 program. It's actually an IND and is an important program. We have a potent and selective degrader here, but we believe that the first-in-class molecule, the Sanofi degrader, is not able to achieve complete degradation in the target tissue, but we believe this molecule, from what we've seen so far, is likely to. We have over 90 patients enrolled, and we expect POC for tissue PD in the second half of 2025. At this point, I'd like to hand off to Aaron Rosenberg, our CFO, to talk a little bit about our third priority for the year. Thank you.
Thanks, John. And moving to our financial performance, 2024 was a pivotal year of growth and an affirmation on our path to sustainability. We have generated exponential top-line growth since 2019, powered by the tremendous global launch of Brukinsa. And we are still in rapid growth phase with Q3 2024 product revenue growth of 67% compared to Q3 of last year. Our strong growth and disciplined investment has resulted in significant operating leverage. And as a result, we've dramatically lowered our operating losses in 2024 and have achieved two consecutive quarters of non-GAAP operating income. This execution is driving a strong financial profile, enabling us to have the freedom and flexibility to control our own destiny. John spoke about what makes our business model truly unique. We have the capabilities of a large pharmaceutical company with a market cap of a mid-cap biotech.
And this enables us to stand out among our peers in terms of our growth profile on an already meaningful revenue base with visibility toward margin expansion and cash generation while building leading and sustainable franchises in large markets such as CLL, supplemented by the optionality that comes from our growing, internally developed, and fully owned pipeline. We will continue delivering on our mission with urgency, and are confident the market will increasingly recognize the value of what we have built and what is to come. We have emerged as a global oncology leader, which is reflected in our increasingly diverse revenue mix. The United States now is greater than 50% of our global sales, and Europe has grown to approximately 10%, and we are still in the early stages of product life cycles in Europe and other key markets such as Japan, Korea, and Brazil.
Our planned re-domiciliation to Switzerland represents another milestone in our growth story. Switzerland is a major life sciences hub with some of the world's most innovative biopharmaceutical companies calling Basel home. And we look forward to taking our leadership place in this dynamic and important region. We continue to mature in terms of our financial performance and how we communicate with our valued shareholders. We will commence quarterly earnings calls beginning with our Q4 results in late February. And at the same time, we will issue 2025 guidance on the top and bottom line. In terms of performance, we anticipate significant product revenue growth as we continue to expand market share across our portfolio and launch Brukinsa and Tevimbra in new markets. And we anticipate this will translate to meaningful cash flow from operations. And finally, we expect to reach full-year GAAP operating income breakeven in 2025.
Before I hand the floor back over to John, I just want to highlight a few of our key pipeline value inflection points. For our commercial assets, you will note important 2025 milestones, including Tevimbra approvals in key markets such as Japan. Our late-stage hematology assets have a number of significant milestones in 2025, including phase II trial readouts that may support accelerated submissions, as well as the initiation of phase III pivotal trials for both sonrotoclax and our BTK degrader, including our planned head-to-head trial versus pirtobrutinib. Turning to our early-stage pipeline, as you have heard, we have a number of proof of concept catalysts expected for our early pipeline across multiple modalities and therapeutic areas. Having so many value creation opportunities in large target markets puts us in an enviable position. We look forward to sharing more data in future updates.
With that, I'll hand it back over to John.
One more slide, I promise. Five years ago, I want to leave you with a snapshot of how much we've changed in just this period of time. And then I want to ask you to imagine where we might be in five years. We've undergone a remarkable transformation in that time, becoming a fundamentally different and more powerful organization. Back in Q4 2019, which was the quarter we launched Brukinsa in the U.S., we reported only $1 million of Brukinsa revenue. We had just six active molecules in clinical development. But by Q3 of this year, the global Brukinsa sales soared to $690 million, driving total revenues to an impressive $1 billion. Our profitability and our cash profile underwent a complete turnaround, reflecting the strength of our business model. And today, our R&D pipeline boasts more than 30 active molecules in development, underscoring our commitment to innovation.
Really, as we set our sights on the next five years and beyond, the question really remains: What new milestones will we achieve together as BeOne, delivering on our mission to expand the highest quality therapies to more people around the world? We're doing this through courage, persistence, innovation, and by challenging the status quo. And personally, I believe you're going to see an organization that does become one of the most impactful oncology organizations and is well-known for its strength and leadership, both in protein degradation in ADC and in bispecific, trispecific. Thank you so much.
So we'll start with a couple of my questions. And I think we introduced John and Aaron, but we're also joined on stage by BeiGene's global head of R&D, Lai Wang. So maybe for Lai or for John, how has BeiGene been able to build a pipeline spanning multiple modalities? You talked about small molecules, degraders, ADCs, bi- and trispecifics. And I guess, what gives you the confidence that you as a company can be highly competitive across all these different areas?
Yeah, thanks for the question. Especially the cancer. Cancer is a very complicated disease. So in order to really tackle cancer, this major, major health issue, you have to base on science, based on the right target. While one size doesn't fit all, not all the targets can be addressed in the same way. So probably about five years ago, BeiGene really began to invest heavily into different technology platforms. John talked about some of them. So for example, for degrader, BeiGene right now has about 16 degrader programs in our pipeline, including three in the clinic. Truly makes us one of the probably a power player in this space. And the degrader is fascinating. We probably don't have enough time to go through them. We truly believe degrader is probably the future for small molecules because it brings additional benefits compared to traditional kinase inhibitors, etc.
So on the biological side of it, this year alone, we take three ADC molecules from our own pipeline into the clinic. Right now, in the preclinical setting, we have 19 ADC molecules with major focus on bispecific ADCs as well as new payloads on the ADC side of it. It's an exciting time for us on the ADC as well. In addition to that, we're also investing in the T-cell engager, bispecific, trispecific. We believe technology, if you win on technology, you can win this game. Just add on to that, BeiGene really wants to take a portfolio approach to tackling the different types of tumors. You see what we did with CLL. We believe we can reproduce that with other tumor types, and to achieve that, you really be able to execute them perfectly in the clinic. John showed you one of the examples, CDK4.
That was only about one year. We were able to enroll over 130 patients for phase I first-in-human study, with on average six weeks per cohort. In addition to the early clinical execution capability, we recently finished a phase III, a global phase III on the CLL side of it. It's 640 patients close to finished, 640 patients in 20 countries, over 200 sites in about just one year, and the vast majority of patients were enrolled outside of China, so we believe with the ability to create best-in-class molecules, first-in-class molecules associated with clinical execution capability will really help us to fight against cancer.
Maybe for John, what's your business development philosophy? This is a company that we know you've had success with some beneficial agreements in the past. Is there any appetite to either in-license or out-license assets from here?
Sure. We love deals, and we're pretty good at them. I think from an in-licensing perspective, we look at a lot of things. We have a lot of interest. This MAT2A fit well with our internal program, and we brought it in. From an outbound perspective, I would like to remind people in that five-year period, we actually generated $1.2 billion in upfronts and milestones by partnering out our PD-1 and our TIGIT. Now, that more than paid, I think it was like a 50% return on all of the research we did during that time. So we certainly have a history of doing deals. We plan on continuing to do deals. We do believe we have this incredibly robust pipeline now with lots of the most compelling early things in oncology.
We certainly are very open to sharing the upside and the development of those with major companies and involved in that. We do anticipate that, knock on wood, we're going to have an embarrassment of riches. When that's the case, you do want to work with other people and find clever ways to push everything forward as aggressively as possible. Yeah, we're very open, very active, and we have a lot of interest in many of these programs and many of the programs that aren't profiled in those top six that are still in the clinic from third parties.
Great. And maybe for Aaron, I think at one of the last slides, you talked about 2025 is the year of breakeven. How do you think about balancing this kind of progress towards profitability with investing behind the commercial assets and in the pipeline?
Yeah, great. And thanks for the question. And it is a balance. I'd say first, I would start with the amount of growth that we're experiencing as a company. The incredible momentum that we have on the top line allows us to continue to invest for growth. And I think you see that in the recent performance. And while we do that, as I spoke, we are realizing significant operating leverage and allows us to foreshadow where we anticipate we will be this year. That being said, we are very keen on delivering our mission and maximizing our assets. And fortunately, we have a pipeline that allows for that flexibility and optionality. As you think about the R&D investment, I would remind everyone that we do have a portfolio of late, mid, and early stage of assets.
So the investments that we're making in our current late stage and commercial assets, the investments, for example, in a Brukinsa or a Tevimbra, those incremental investments will roll off over time, which provides headspace for the early pipeline to come through. So I think from our side, it's really a dual mandate. It's how do we continue to invest in the business while driving to long-term profitability? Because that is the true measure of sustainability, cash generation. And this is a company and a mission that we believe in for the long run, and that's our intent to manage it that way.
Great. Well, thank you.