BeOne Medicines AG

Good day, everyone. Welcome to Beijing's Q4 and full year 2024 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.

Good morning and welcome. Thanks for joining us today. I'm Dan Maller of Investor Relations at Beijing. 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.beijing.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 the forward-looking statements as a result of various factors, including those risks report filed with the SEC. Please also carefully review the forward-looking statements disclaimer and 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 our earnings release. 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. Now turning to today's call as outlined on slide three. John Euler, our co-founder, chairman, and CEO, will provide opening remarks and an update on our hematology franchise. Matt Shawless, our general manager of North America, will provide an update on the U.S. commercial performance of Rukinza. Lai Wong, our global head of R&D, will discuss our R&D and pipeline progress. And Aaron Rosenberg, our CFO, will review the fourth quarter financial results and our 2025 financial guidance. We will then open the call to questions. I'll now pass the call over to John.

Thank you, Dan, and good morning, everyone. 2024 was a truly remarkable year in which we achieved $3.8 billion in revenue for the full year, $1.1 billion in Q4, positive quarterly cash flow from operations, BTKI leadership in new patient starts across all lines and all indications in the U.S., and Brukinza U.S. revenue exceeded Calquence for the first time in the fourth quarter. We introduced 13 new molecular entities into the clinic, and we matured as a global company, with the completion of our 800 million U.S. flagship manufacturing facility, our ticker change to ONC, and our proposed name change to B1, and redomiciliation to Switzerland. We believe that we've reached an inflection point, and we're truly excited for the future. Our company was purpose-built to address the long-lived challenges of return on investment in our industry, and 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 develop and commercialize an oncology medicine, and they're now estimated to be $250,000 to $300,000 per patient, still rising. It's increasingly challenging out there. But we built Beijing from inception for a world that envisioned these challenges. Our truly global, CRO-free clinical team of nearly 3,700 allows us to move at a greater speed and a lower cost than our industry peers. Paired with our internal research and internal manufacturing, we've enabled a fast proof-of-concept approach, that shaves meaningful time from early stage development. We're innovating with intentionality, and we're building best-in-class franchises with better outcomes for patients that will provide superior returns in the increasingly competitive commercial landscape. In CLL, we believe we're in the middle of a once-in-a-lifetime opportunity, which is akin to that of Gilead in HIV and Vertex in cystic fibrosis. Our focus for 2025 is to deliver upon three strategic pillars. First, solidify and deepen our hematology franchise leadership. Second, advance our pipeline of internally developed assets. And third, drive superior financial performance. My section today will focus on our heme franchise. And of course, we can't talk about the franchise and our heme leadership without starting with Brukenza. Brukinza was designed from inception to provide 24-7 inhibition of PTK in all disease compartments and to address efficacy and tox challenges of Ibrutinib. As you can see here, only Brukinza maintains serum exposures well above its IC50, whereas Ibrutinib and Acala exposures are well below their IC50 for the majority of the period. And you can't fight cancer part-time or only in the blood. A recent peer-reviewed publication analyzed the differences in VTK occupancy between the three approved covalent VTK inhibitors. These results indicate to us that with regard to target engagement, only ZANU provides complete and sustained inhibition of VTK across all relevant disease compartments and that ZANU is greater than Ibrutinib, which is greater than Acala. These data and the clinical results shown here proved our hypothesis was correct. In the Alpine trial, Brukenza demonstrated sustained superior PFS efficacy in lower cardiac tox head-to-head against Ibrutinib. On the left, the Alpine data in the high-risk deletion 17P P53 subpopulation is shown At 42 months, milestone PFS was 59% for ZANU and only 32% for Ibrutinib. On the right is the ElevateRR study, also in the high-risk deletion 17P P53 patients, which is said to have a hazard ratio of 1. But please note the early separation is likely due to lack of tolerance to Ibrutinib. But more importantly, that Acala crosses at just over 30 months and actually becomes 8% worse than Ibrutinib at 42 months. And at this time period, the milestone PFS is only 28%. Yes, I said 28%. And this compelling data has led to exponential growth in Brukinza global sales. less than two years from our first approval in CLL, and despite being the third to mark it, Brukenza has become the BTKI class leader for new patient starts. Perhaps the combination of the aforementioned data and real-world experience are leading to both patients and clinicians understanding that on efficacy, C is greater than I, which is greater than A. I'd like to take a few moments to talk about the fixed duration treatment landscape and why we view it as a key opportunity to grow our CLL leadership. To create compelling fixed duration therapy, three key attributes are required. First, deep response. Second, impressive and sustained PFS compared to continuous therapy. And third, safety during the treatment period, but adds only minimal liability over a continuous Brukinza, which has consistently demonstrated a favorable safety profile. Recent data presented by competitive treatment options certainly leave a lot to be desired. First, Amplify did not show a deep MRD response. Actually, only 34% of AV patients reached MRD negativities. which was both statistically inferior to chemo and also dramatically worse than precedent data from similar Phase III trials of VO and VI. By comparison, our combination of Brukinza plus Sonro has shown 91% MRD in a much less healthy all-comers population. Secondly, current fixed duration options do not show a sustained PFS benefit that matches continuous-use Brukinza, particularly with longer follow-up. Amplify enrolled a highly selected, young, and fit population. The population represents less than 25% of real-world CLL patients. So how did AV compare to the precedent similarly fit VO data? It's simply much worse. How did A compare to I when they each combined with V? The A combination was worse in both MRD and in PFS, despite being in a fit population versus VI's unfit population. Numerically, in combination, I was greater than A, which is consistent with all the previous data. And this is even more striking as one expects FIT to do better than unfit. How much better might one expect? For VO, the data is right here. Recognizing the limitations of cross-trial analyses, there appears to be a 6% to 7% improvement in PFS benefit when comparing FIT versus unfit. The underwhelming efficacy of Amplify becomes even more evident when reviewing the actual PFS curves at the early 36-month period, no Brukinza in the unfit population at 84%, and A plus B in fit patients at only 76.5. Also notice AB shows further deterioration around that time point. And finally, current fixed duration options have a challenging safety profile during the first 60-week treatment period compared to Rutenza. And that's comparing, again, unfit to a highly selected healthy population. As you can see, there's a substantial additional tox burden placed on these elderly patients during the first 60 weeks, all for an inferior 36-month PFS. It raises the question for AV, is the juice worth the squeeze? We strongly believe in the promise of fixed duration, but unfortunately the current options don't fulfill this promise. This provides a significant opportunity for a best-in-class combination of Sonro and Xanu that checks all the boxes, deep MRD responses, impressive and sustained PFS curves in 19 months, and acceptable safety. This combination has the potential to render the competitive molecules as not credible substitutes. Our Phase III pivotal celestial CLL trial has completed enrollment against V plus O, not against chemo, and V plus O is actually a relevant and widely used standard of care. We also have an ongoing Phase II studies with early registrational potential in CLL, Waldenstrom, and MCL, and we're planning to initiate two additional Phase III trials in CLL and MCL in the first half of this year. Another big EEM opportunity is our BTK CDAC. This program has enrolled more than 500 patients and is by far the most advanced BTK to greater. We presented compelling early efficacy and safety data in a heavily pretreated population at ASH. As you can see here on the slide, the evolution of our data relative to PERTO together with KOL feedback gave us confidence to initiate a head-to-head Phase III trial against PERTO in the second line later this year. We also have an ongoing Phase II expansion trial in relapsed refractory CLL that's potentially registration-enabling and have aggressive development plans for earlier lines of therapy, including combinations. We are really excited about this program. In summary, our EAM franchise is poised to win. as we are the only company with the wholly-owned potential best-in-class molecules across the most important targets and modalities. We believe that we can dramatically improve the standard of care across all lines in CLL. We have a once-in-a-lifetime opportunity to build life-changing combinations in the preeminent franchise in the $12 billion-plus CLL market, and we believe our franchise model will help insulate us. And with that, I'll pass it over to Matt.