Good afternoon, and good morning, everybody. It's a great pleasure to be with you today, and I welcome you to our next investor webinar of our Pharma division. With this second webinar this week, we continue our series of events to keep you appraised of key developments and milestones across the group. Following our webinar on Kerendia in November last year, we today focus on our second promising launch asset, Nubeqa or darolutamide. Last night, detailed study data of ARASENS, our phase III trial that examined the efficacy and safety of darolutamide to treat prostate cancer in a late stage of the disease, have been presented at the ASCO GU for the first time. We will put these data into perspective with existing treatment options and discuss how the broadened clinical profile of darolutamide can change the treatment paradigm in prostate cancer in the future. Finally, we will give an update on our further development program and the commercial potential of darolutamide. I'm delighted that the coordinating principal investigator of the ARASENS study, Dr. Matthew Raymond Smith, is joining our webinar today. He will talk you through the study data he presented at ASCO GU yesterday in all detail. A very warm welcome again, Dr. Smith, from my end. Before we dive into ARASENS, Christian Rommel, our Head of R&D at Pharma, will kick off this webinar with an overview of Bayer's overall strategy in pharma and the oncology space. Robert LaCaze, our Head of the Oncology Franchise, will then address the indications and unmet medical needs in prostate cancer and darolutamide's position in this market today. Following Matthew's presentation, Robert will then finish up with a summary of the commercial implications of darolutamide's clinical profile and our future ambitions. Today's webinar is scheduled for one hour. The presentation should be done within, I think, the first 35 minutes, roughly, and for the remaining 25 minutes, you will then have a chance to raise questions. You will find instructions for the participation in the Q&A session in the Zoom chat, as we normally show the instructions there. I will remind you of those later again. As always, before we begin, I would bring your attention to the forward-looking statements included in the materials today and currently on the screen. With that, the floor is yours, Christian. Thank you, Oliver, for your introduction, and welcome everyone. At Bayer, our focus is crystal clear on patients and patients' medical needs. We aim to provide impactful solutions to prevent, diagnose, treat, or potentially cure diseases with increased precision and personalization. Cardiovascular diseases, women's health, and oncology remain central to our R&D efforts. We bring decades of scientific excellence to the fields where, despite significant progress, there remains considerable unmet need. Our recent new drug launches in heart failure, Verquvo, in kidney disease, Kerendia, and in prostate cancer, Nubeqa or darolutamide, each offer significant new treatment options to patients. We have bold ambitions in oncology, and today we have an opportunity to provide an update on the significant progress we've made with Nubeqa. That said, we are not limited by our traditional strongholds. We apply our expertise wherever we see an opportunity to make the difference to patients across rare diseases, ophthalmology, and also in some of the most challenging neurological disorders. Now, our aim is to address unmet medical needs with innovative, differentiated medicines that reach patients as fast as possible. Precision medicines and more targeted personalized therapies will feature even more prominently in our future pipeline, not just in the rapidly growing oncology franchise, but also across cardiovascular, kidney diseases, and as mentioned, beyond. Now, life sciences and healthcare are transforming at an amazing speed and scale. Rapid advances across human genetics, genomics, molecular biology, combined with data sciences and the technological progress, is driving more personalized medicines and new opportunities to improve the health. We are excited to be part of this extraordinary area of scientific and medical progress. At Bayer, we invested boldly in new science and technologies like gene and cell therapies, yet are also building on our leadership in small molecule chemistry and radionuclide therapies, building on the legacy of Algeta. Insights into underlying human disease biology drives us to use whichever of these tools is best suited to this challenge. We are inspired and enabled by technology, not constrained by it. We continue to develop our AI and digital health capabilities. Digital tools, of course, help patients to better manage their conditions, enable more convenient care delivery, and are really revolutionizing data collection. Clinical trials can be, by those means, can be faster, more targeted, and less burdensome for our patients. Rapid analysis of large volumes of data, including real-world data, provides new insights into health and disease. Now, with this context, let's move into oncology and Nubeqa. We are excited about the opportunity of Nubeqa making a difference to prostate cancer patients and the impact on our growth strategy and ambition in oncology. Nubeqa builds on our track record of delivering innovative cancer medicines in prostate cancer, such as Xofigo, or precision medicine such as Vitrakvi. There are three areas for us that have the potential to address the remaining unmet need in oncology. Targeted radiopharmaceuticals with the focus on targeted alpha therapies, immuno-oncology, including cell-based therapies, precision molecular oncology, and today we are going to show you a powerful example with Nubeqa in that area. However, we also have a promising early clinical stage asset with EGFR exon 20 inhibitor, which we will continue to work on this year. Connected to precision molecular oncology is also Bayer's recent exciting strategic move of acquiring Vividion Therapeutics, and by this its chemoproteomics platform that can unlock such so far untrackable target space. In the area of targeted alpha therapy, there is an emerging class of novel radionuclide therapies that have the potential to become a powerful tool to help physicians fight cancer types that are rather hard to treat. We are working on novel conjugate approaches, where we combine different alpha radionuclides with different targeting moieties, including antibodies and small molecules. An example is with the acquisition of Noria and PSMA Therapeutics last year. We invested here further into the area of targeted alpha therapies, expanding our capabilities now to the next generation approaches using actinium and a new small molecule PSMA- targeting technology that has significant potential to reduce some of the off-target toxicities, for instance, salivary glands and in organs like the kidney that has been observed with other PSMA-targeting molecules. Our third pillar, immuno-oncology. Here we are harnessing the most powerful tool there is to fight tumor cells, the body's own immune system. One example of our rather focused immuno-oncology portfolio is a small molecule inhibitor blocking the AHR pathway, which is believed to be a key player in helping the tumor cells to evade immune response or immune escape. The success of our launch products, together with our main inline brands, support our innovation strategy, enabling future sustainable growth of our oncology business at Bayer. Now, with some details to the approach of the strategy with Nubeqa. Despite significant advancements in the treatment of prostate cancer patients, there is still a high unmet medical need. Targeting the androgen receptor, AR, in prostate cancer, the so-called key oncogenic driver, which means it's consistently and uniformly expressed across cancer cells of the tumor tissue, is genetically, scientifically, and clinically validated therapeutic approach. From a patient's perspective, as shown in the illustration on the left-hand side, this approach typically follows chemical castration with androgen deprivation therapy or surgical castration. Key focus in cancer treatment is to extend overall survival and delay development of metastases, limit additional toxicity burdens, and maintain lifestyles, the quality of life, often asymptomatic, fit, and active men, and manage comorbidities and limit drug-drug interaction that can lead to change in the efficacy and safety of patients' ongoing medications as well as combination opportunities. Multiple ways exist to therapeutically target the androgen receptor biosynthesis and signaling axis. Nubeqa is an orally available, highly potent and selective small molecule antagonist, directly inhibiting the gene regulatory activity of the androgen receptor protein in cancer cells. It addresses the need of strong efficacy, while at the same time providing an outstanding tolerability profile, which is the result of its unique and differentiated chemical structure. Let's talk about it in more details. Today, there are three approved small molecule drugs in the market that target the androgen receptor and inhibit the androgen receptor protein activity in prostate cancer cells: apalutamide, enzalutamide, and darolutamide. As can be seen from the illustration on the left-hand side of the slide, apalutamide and enzalutamide are very similar in their chemical structures, basically differing only at the two position that are highlighted here in gray. In contrast, darolutamide, Nubeqa darolutamide, is a distinctly differentiated compound compared to the other two drugs, basically pretty much in gray. It has a different and more flexible chemical structure with a higher polarity and ligand efficiency, as well as an increased hydrogen bond-forming potential. From a medicinal chemistry expertise point of view, tells us that all these factors are associated with low blood-brain barrier penetration, which is clinically relevant and meaningful differentiating feature, and in fact, an advantage of darolutamide. Strong evidence that support this differentiated blood-brain barrier penetration profile comes from qualitative C14 carbon-labeled in situ imaging analysis that we show to the right-hand side of the slide. Here you can see in the illustration the distribution of darolutamide, apalutamide, and enzalutamide, these three molecules in brains of rodents, in this case, rats. Blue color indicates low levels of active ingredients, whereas green, yellow and red indicate higher levels of ascending, in an ascending order. The results show that brain to blood penetration ratios of enzalutamide and apalutamide were 10-fold higher than darolutamide in these preclinical models. In addition, concentration of darolutamide in the brain tissue was about 50-fold lower than enzalutamide and about 30-fold lower than apalutamide. In conclusion, darolutamide is a structurally different androgen receptor inhibitor with low blood-brain barrier penetration shown in those preclinical models. My colleague Robert is now illustrating how this translates into darolutamide's strong and differentiated clinical profile. Robert? Thank you, Christian, and also a warm welcome from my side to the audience today. I'd like to start my presentation with just some general remarks on prostate cancer overall. As you can see from the pie chart, out of the estimated 10 million cancer patients that were diagnosed globally in 2020, one out of seven actually suffers from prostate cancer, making it the second most common cause of cancer in men worldwide. According to 2018 data from GLOBOCAN, it causes, you know, greater than 350,000 deaths per year. Prostate cancer is usually diagnosed in men over 50. The unmet need, though, is actually a vast one, and while the majority of the men are diagnosed with localized disease, up to 40% of these patients can have relapse disease that is ultimately incurable over time. There are a fair number of men also who are diagnosed with locally advanced or even metastatic disease upon first diagnosis. Once the disease becomes metastatic, the five-year survival rates really drop to around 30% or so. Therefore, like all other cancers, it's also very important to get this disease diagnosed at an early stage so that respective therapeutic options can be initiated for the patients. Now, looking into the diagnosis patterns in more detail, prostate cancer can be separated into early, mid, and late stages of the disease. According to the epi numbers, if you look at it from a U.S., Japan, and the top five countries in Europe, around 145,000 patients are actually treated in the early stage or the so-called adjuvant and neoadjuvant setting. In the non-metastatic and the midstage setting, a total of 130,000 patients are treated each year, of which 2/3 are in the biochemical relapse or the BCR area, and 1/3 are diagnosed with non-metastatic castration-resistant prostate cancer. The biggest portion of patients, 220,000, are in the late stage or the metastasis stage of the disease, of which 1/3 is suffering from hormone-sensitive and 2/3 from castration-resistant prostate cancer. Now, as Christian has already shown, androgen receptor blockade has become a standard of care to effectively treat prostate cancer. Based on the strong clinical data of our first trial, the ARAMIS trial, that led to Nubeqa's first regulatory approval in non-metastatic castration-resistant patients in 2019. In this study, Nubeqa demonstrated a strong metastasis-free survival of more than 40 months, equivalent to a 22-month benefit versus placebo. In addition, it showed a hazard ratio of 0.69 in overall survival compared to placebo, equivalent to a 31% reduction of risk of death. This data has also been published in the New England Journal of Medicine, and they compare favorably with the study's results observed in the same indication with enzalutamide and apalutamide. On top of efficacy, Christian also stressed the relevance of, in the unmet need of a drug's tolerability profile. It's potentially even more important in prostate cancer therapies due to the long treatment durations and the fact that many of these patients are still very active, and the prostate cancer oftentimes is still asymptomatic. For this reason, treatment options with a less likelihood of causing a disruption in the patient's day-to-day life due to side effects of the medication are clearly preferred by both physicians and by their patients. As you can see from the tolerability data in the ARAMIS trial, the side effects of darolutamide are very favorable as compared to the placebo arm, consistently and across all relevant dimensions. Summing up ARAMIS, it actually revealed that darolutamide's strong efficacy profile, while at the same time it demonstrated this very positive tolerability profile. These both together make it an ideal treatment choice for patients who suffer from non-metastatic castration-resistant cancer. Now, following this approval, Nubeqa's approval in major countries, we're focused on making Nubeqa available to patients as quickly as possible. In spite of starting many of the launches of the ARAMIS trial and the new indication in the middle of the COVID-19 pandemic, that came with the significant limitations to be able to interact with physicians and payers. In spite of that, Nubeqa has shown a strong successful market launch. Today, our drug is approved in 65 countries. It's available in 32 commercial markets and additional 24 private markets. Pricing and reimbursement schemes has already been established in 32 countries. Nubeqa's strong and differentiated profile is also backed by a series of external validations. We're able to receive approval in China without having local patients. On top of this, Nubeqa is the only second-generation AR to be awarded a considerable benefit rating in the non-metastatic castration-resistant space in Germany by IQWiG and the G-BA. In the U.S., favorable customer perception supports the drug's continued uptake, and we've seen a rapid adoption by the payers with over 90% of the lives covered in managed care. Our market research confirms that Nubeqa's strong value proposition for patients and physicians and the importance of its profile. We find that once a physician uses Nubeqa 3x-4x, they see the benefit in their patients, and it becomes their drug of choice for the indication of non-metastatic CRPC. This is also reflected in our sales numbers for 2021, which came in around EUR 220 million, equivalent to about $250 million. I'd like to conclude the first part of my presentation with a reminder that the clinical as well as the commercial profile of Nubeqa until today is only based on the ARAMIS study and their approval in the non-metastatic CRPC cancer setting space. Now, I am more than happy to hand over to Dr. Matthew Smith, who is the Coordinating Principal Investigator of the ARASENS trial and the lead author of the New England Journal of Medicine publication on ARASENS. Dr. Smith is the Director of the GU Malignancies Program at Massachusetts General Hospital Cancer Center, and he'll walk you through the key data of the ARASENS trial, our second successful phase III study of Nubeqa. This trial examined Nubeqa's use in patients suffering from metastatic hormone-sensitive prostate cancer. Dr. Smith? Thank you, Robert. It's a pleasure to be here and to present the ARASENS data. This is the study design. ARASENS is a global randomized, controlled trial. ARASENS enrolled 1,306 patients in 286 centers in 23 countries. The study included patients with metastatic hormone-sensitive prostate cancer in any ECOG performance status of 0 or 1 who are candidates for androgen deprivation therapy and docetaxel. Eligible patients were randomized in equal proportions to darolutamide or placebo twice daily. All patients in both arms received the standard of care, which is androgen deprivation therapy and six cycles of docetaxel, the latter starting six weeks after randomization. The primary study endpoint was overall survival, and then there were a number of key secondary endpoints. I think when we designed this trial, we took a bold approach saying what would really be important would be to move the needle and improve overall survival, and hence we chose that as the primary study endpoint. Next slide. Here's the most important data. This is the primary analysis for overall survival. This endpoint was pre-specified and event-driven. There was no interim analysis. This is the final analysis. Compared to placebo, darolutamide significantly reduced the risk of death by 32.5%. The hazard ratio is 0.68 with 95% confidence intervals of 0.57-0.80. This is highly statistically significant with a p-value of less than 0.001. You'll note, looking at the shape of the curves, that they separate early and continue to widen their separation over time. The median overall survival was 48.9 months in the placebo group and not yet reached in darolutamide. The four-year overall survival rate was 50.4% in the placebo group and improved to 62.7% in the darolutamide group. Next slide. This clinically important and statistically significant improvement in overall survival was observed despite a high rate of subsequent life-prolonging therapy in the placebo group. One of the general concerns in interpreting trials of this type is that if patients in the placebo group did not have access to subsequent therapies, the benefit may not be generalizable to settings where such therapies are available. It's very reassuring here that a high proportion of patients in the placebo group received subsequent life-prolonging therapy. More than 75% of patients in the placebo group received subsequent life-prolonging therapy. The most commonly administered life-prolonging treatments were abiraterone acetate, enzalutamide, cabazitaxel, and docetaxel. 2/3 of patients in the placebo group, by the data cut-off date, had received subsequent life-prolonging therapy with one or more androgen receptor pathway inhibitors. Next slide. There was consistency of the overall survival benefit in the pre-specified subgroups. We also saw consistency of the OS benefit by metastatic stage at initial diagnosis. For patients with de novo metastatic disease, meaning metastatic disease diagnosed at the time of initial prostate cancer diagnosis, the hazard ratio was 0.71. For those with recurrent metastatic disease, the hazard ratio was even lower at 0.61. Next slide. We also saw a benefit across key secondary efficacy endpoints. Time to castration-resistant prostate cancer and time to pain progression were significantly longer in the darolutamide group than in the placebo group, with hazard ratios of 0.36 and 0.79, respectively. Next slide. Darolutamide also improved time to first symptomatic skeletal event and time to first subsequent anti-neoplastic therapy with hazard ratios of 0.71 and 0.39, respectively. Next slide. Consistent with the clinical experience in other settings, darolutamide had a very favorable safety profile. The rates of any treatment-emergent adverse events, serious adverse events, and adverse events leading to permanent discontinuation of study treatments were similar between the darolutamide and the placebo groups. Next slide. As expected, most of the Grade 3 and 4 adverse events we observed in both arms were attributed to docetaxel chemotherapy. Those included neutropenia, febrile neutropenia, and anemia. Importantly, rates of these Grade 3 and 4 AEs were similar between the darolutamide and placebo groups. Next slide. Robert described the specific benefits of darolutamide in terms of its safety relative to other AR pathway inhibitors, but certain adverse events have been associated with AR pathway inhibitors as a drug class. Although it's important to note that those rates of AEs of special interest vary considerably for different drugs within that class, and that's specifically true for darolutamide. These AEs of special interest for the class include fatigue, falls, fractures, rash, hypertension, certain cardiac disorders, and central nervous system disorders. After adjustment for drug exposure, though, the rates of these AEs of special interest are similar and really indistinguishable between the darolutamide and the placebo groups, sort of reinforcing the favorable safety profile that was observed in ARAMIS. Next slide. In summary, darolutamide in combination with ADT and docetaxel significantly improved overall survival in patients with metastatic hormone-sensitive prostate cancer. Darolutamide reduced the risk of death by 32.5%. Darolutamide improved OS despite a high rate of subsequent life-prolonging systemic treatments in the placebo group. The OS benefit for darolutamide was consistent across the pre-specified subgroups. Darolutamide also demonstrated significant improvements in key secondary efficacy endpoints, including time to castration-resistant prostate cancer, time to pain progression, time to first SSE, and time to first subsequent antineoplastic therapy. Consistent with the prior experience with darolutamide in non-metastatic CRPC, the rates of adverse events were similar between the darolutamide and placebo group. I conclude that based on the results of ARASENS, darolutamide in combination with ADT and docetaxel should become a new standard of care for the treatment of patients with metastatic hormone-sensitive prostate cancer. Thank you, Dr. Smith for that great overview of the ARASENS data. For those of you who maybe had missed the presentation yesterday, you can also find the full publication in the, it was also published in New England Journal yesterday afternoon as well. Dr. Smith is the lead author on that paper as well. You know, as Dr. Smith has shown, this is actually the second-largest phase III trial for darolutamide that's demonstrated a major overall survival advantage, while at the same time providing for a really favorable tolerability profile for the patients. It's important to stress again that the high efficacy and the tolerability hurdles in the ARASENS trial. This is a study where we actually combined ADT therapy in addition to chemotherapy in both arms. None of the existing novel hormonals have demonstrated this level of clinical benefit in a phase III trial. Keep in mind that over 75% of the patients, as you saw from the data with Dr. Smith in the control arm of the ADT and chemotherapy, also received additional substantial life-saving drugs, including enzalutamide, abiraterone, and chemotherapy. You know, making the efficacy data of the darolutamide in combination with chemo and ADT even more remarkable in this ARASENS study. You know, the secondary endpoints also were impressive and of note. This was also discussed a little bit in the discussion yesterday in the presentation. The time to castration-resistant prostate cancer was reduced by 64% with a hazard ratio of 0.357. The risk was reduced by 64%. In the control arm, patients became castration-resistant in a little over a year and a half or 19.1 months, while patients in the Nubeqa arm still had not reached the average number of months to becoming castration-resistant. Many of these patients have been on study for 3.5-4 years. You know, at the time of the data cutoff on October 25th, 2021, the average length of darolutamide therapy was 41 months compared to the control group of 16.7 months. While there was a significant overall survival advantage, as you saw from the presentation, the addition of darolutamide to chemotherapy did not introduce additional major toxicities for the patients beyond chemotherapy. Again, this underpins the ease of use of Nubeqa, even when it's used in combination. With this strong co-confirmation of efficacy and the tolerability profile in two major studies in two different settings, we feel that darolutamide can become a foundational therapy in prostate cancer across the different stages of prostate cancer given this unique profile. Now, over the next few years, we'll continue to invest and generate data to allow darolutamide to fulfill this mission of becoming the foundational therapy across a broad spectrum of prostate cancer. As you can see, with the development program, which includes five major phase III studies, two of them already been completed and three more in progress. In the adjuvant setting, we're doing the DaSL-HiCap trial, which is expected to show results in the 2028 timeframe. We're also, you know, this is part of the announcement that we'll be doing a Biochemical Relapse study as well, the BCR study. We plan to start this trial in the second half of this year, with results expected in 2027. Finally, we have an ongoing trial, which is really the sister trial to the ARASENS trial. It's called ARANOTE. This is also in the metastatic hormone-sensitive space where Nubeqa is given as a single agent with ADT as compared to placebo and ADT. In summary, our investments are aimed at generating data across the early, non-metastatic and the metastatic settings, both with and without chemotherapy. As the novel hormonals continue to move in the earlier settings of this disease, it's important to have a profile like darolutamide that combines an efficacy profile with an excellent tolerability profile, as most of these patients in this earlier setting will be asymptomatic. Lastly, darolutamide's combinability profile will also consider additional combination trials with other emergent agents if the science is clear. With the confirmation of darolutamide's clinical profile and expansion into the metastatic setting, as well as the investments that we're making in the additional clinical trials, we feel that darolutamide has the potential to generate sales, peak sales of more than EUR 3 billion. The next step for us, though, is to rapidly file the ARASENS data as quickly as possible, to gain the regulatory approval in the metastatic hormone-sensitive prostate area, and extend our existing label in all major markets to make the drug available to patients as soon as possible. As you can see from the chart, we're just weeks away from simultaneously filing in the U.S., Japan, and the E.U., and China is just a few weeks behind. Putting today's presentation into a broader context and closing the loop from what Christian started with his remarks at the beginning of the webinar, our ambition is to become one of the top 10 oncology companies by 2030. Over the last five years, we've made decisive steps toward that goal. We've more than doubled the number of marketed products from three to six. We've gained more than 75 commercial approvals across multiple indications and tumors. In addition, in terms of the innovation, we've seen three FDA breakthrough designations. We have 15 ongoing registrational studies. In addition, we've entered into newer platforms such as precision oncology, as Christian stated, which was strengthened by our acquisition of Vividion last summer. We've also expanded our radiopharmaceutical approaches with the addition of Noria Therapeutics and PSMA Therapeutics, which occurred last spring. On top of this, we continue to explore the next generation of immuno-oncology with cell therapy partnerships. Finally, with the launches of Vitrakvi and Nubeqa, we have translated compelling medical profiles into commercial success. Vitrakvi is the first drug to receive a global tumor-agnostic approval in both pediatric and adults. We're also committed to making Nubeqa the standard of therapy in prostate cancer. With these investments and the continued growth in Nubeqa, oncology is planned to become a key growth driver for Bayer Pharma. Now this concludes my part of the presentation, and I'll hand it back over to Oliver to open it up to Q&A. Oliver? Thank you so much, Robert, Dr. Smith and Christian, all for your presentations. With that, let's move to the Q&A. Before we start, as always, some housekeeping items on the Q&A session from my end. If you have a question, please click on the Raise Your Hand icon. If your question has been answered or you wish to cancel your request, please click the Lower Your Hand icon. When you will be called to ask your question, you first have to unmute yourself by confirming the corresponding prompt that will appear on your screen. If you have joined the conference via telephone, the procedure is slightly different. Please press the star followed by the nine on your telephone to queue for asking a question. When you're being prompted to ask your question, please press the star followed by the six to unmute yourself. I see we have the first questions coming in, and I think the first question comes from James Quigley from Morgan Stanley. James, you're next. You're first. Hello. Thank you for taking my questions. So just in the terms of the new peak sales guidance, could you give us a bridge of how you get there from the $1 billion to the $3 billion? Which of the sub-indications are the biggest contributors? And then also sort of related to that, could you remind us of when the patent expires for Nubeqa? I think from memory it's around 2030 in the U.S. But how are you thinking about the adjuvant and the biochemical relapse setting, if they're reading out in 2028 and 2027, how that could impact the peak sales? Yeah, James. This is Robert. I'll be happy to address those for you. As we look at this market space, there's a couple of things that's going on here. Obviously, as the patient population begins to or continues to age, we know in the epi numbers that there's about 1.5% of new patients coming into the space every year with prostate cancer. We know that as you look at the compounds, as Nubeqa, you look at the earlier stages of the disease, patients stay on the drug for quite a period of time. When you look at the metastatic disease, we're quite surprised at the overall outcome that we're seeing in the clinical benefit of the program, and patients will stay on the drug for potentially two, three or even four-plus years. As I showed at the beginning, you look at the different segments of the prostate cancer area between the early, the mid, and the late stages of the disease. We'll have programs in all of those diseases. I won't necessarily give comment on which one of those will be the bigger segments because I think some of those segments will continue to evolve over time. I will say that, if you look at the growth of the market and then the clinical data that we're generating across all the stages, we're quite comfortable in the $3 billion. The $3 billion though is not tomorrow or the next day. It's, you know, more towards the end of the 2027-2029 timeframe, as we do generate the data and the new indications. The patent lives are, you know, depending on which country, ranges from 2030- 2034, I believe, or 2035 timeframe. It does range across, depending on which country or which market they're in. We're very excited about the data, the second large study. Obviously, our goal is to try to have, you know, every couple of years a new bit of data set of studies coming out to continue to fuel the clinical profile, which hopefully will translate into the patient benefits and then eventually into the peak sales. That's great. I'm gonna ask another question if that's okay for Dr. Smith, and just in thinking about the hormone-sensitive or metastatic hormone-sensitive prostate cancer, your patients. What role does chemotherapy play in your treatment decisions? I'm just trying to get a sense of what proportion of your patients are already taking chemotherapy plus androgen deprivation versus that are already on a androgen receptor inhibitor plus androgen deprivation. Just a sense of are there a bunch of patients where you can add on Nubeqa with chemotherapy quite quickly? Or is it gonna be more of a sort of deciding which approach would be best? Thanks. Yeah, good question. Currently the question is, you know, which patients do you intensify therapy for metastatic hormone-sensitive disease? The second question is which agent? Is it gonna be docetaxel or an AR pathway inhibitor? Those vary according to geographic region. In the United States, the patients who have intensified initial treatment typically get an androgen receptor pathway inhibitor. It's a smaller group who receive chemotherapy. Usually the worst prognosis patients. Let me answer it this way. For a patient who's gonna receive ADT and docetaxel, the addition of darolutamide is the easiest decision in the world. The results of ARASENS are compelling. The magnitude of the benefit probably exceeds, in my opinion, the benefit of giving the patient chemotherapy. That's easy. The other sort of knock-on effect of this is gonna be that this compelling data from ARASENS confirms the very strong results from ARAMIS. While these individual like disease states have an important sort of role in like drug approvals and regulatory issues, the field is kinda moving away from that 'cause all the consistent data is saying intensified androgen deprivation therapy or enhanced androgen deprivation therapy improves outcomes across the entire spectrum of prostate cancer. You know, one of the terms used earlier is that, you know, AR is the key oncogenic driver. It couldn't be more true. Our approach, you know, is gonna really be. The thing that wasn't yet said is while there are several other drugs in this class, there's tremendous cross resistance between the agents. It's really gonna be which one do you choose and why do you choose it. Now we have two compelling phase III studies showing an OS benefit, non-metastatic CRPC, metastatic disease, hormone-sensitive disease, and really compelling safety data that, in my opinion, makes darolutamide best in class. That will be my go-to drug in patients who I'm gonna add an AR pathway inhibitor. I think that, you know, that's the choice that the clinicians are gonna be making. You can get very granular and say this indication, that indication, but it's the totality of evidence and really, no other target has shown such consistent results across the entire spectrum of prostate cancer. Right. Thank you so much, Dr. Smith. Thank you. I think next question comes from Michael. Michael Leuchten from UBS. Michael, you're next. Thank you, Oliver. Just going back to that last question, Dr. Smith. If we look at the presentation at ASCO GU, I think there were some slides from the discussant saying that only about 1/3 of patients in the hormone-sensitive setting are actually getting doublets at the moment. It's not a large number of patients relative to what the data like STAMPEDE and LATITUDE would suggest to us. And I think some of the question is, you know, what does chemotherapy really add? As we think about the upcoming data with the ARANOTE trial, do we get to a point where we actually know what the treatment pathway is going to be in this hormone-sensitive setting? That's question number one. There's just a clarification question on the tolerability in the remarks. There was something about adjusted for drug exposure. There were similar rates of adverse events. I just wondered if you could clarify that statement. I didn't quite understand what that meant. Thank you. Yeah. Let me start with the second question 'cause it's more straightforward. Actually, in saying that, I actually understate the safety of darolutamide because the uncorrected rates of those adverse events are remarkably similar across almost all of the AEs of special interest. But just for conciseness, if you would, after adjustment, basically every one of those AEs of special interest becomes similar or more or less indistinguishable between the groups. Both the unadjusted and adjusted rates of AEs of special interest are similar between the groups with a couple of minor exceptions. There's a little bit more rash if you don't adjust for exposure, and I think maybe a little tiny bit more of hypertension. The other question is, like, I think the way. Again, I'll restate it, like AR is a key oncogenic driver in prostate cancer. I think that you're absolutely right that the adoption of intensified systemic treatment for metastatic hormone-sensitive prostate cancer has been slow. That will change over time as the data's accumulated. Candidly, CHAARTED kind of confused the whole field because the initial intensification was with chemotherapy, and then there was this division between high volume and low volume. There's a lot of confusion in the field, and I think that's contributed to the slow adoption. But w ith consistent data about improved overall survival, I see that improving over time. At least in the U.S., the priority is gonna be to add an AR pathway inhibitor. The secondary question will be, you know, in which patients do you also add docetaxel. Like, as is true in all cases in medicine, we're never gonna have all of the data we'd like to make those decisions. Not every single decision we make will be perfectly evidence-based, but there's a compelling body of data to say that we should be intensifying systemic therapy in the vast majority of patients with metastatic hormone-sensitive prostate cancer. At least in the United States, the priority is gonna be the addition of an AR pathway inhibitor. As I have already said, in my practice, my drug of choice is darolutamide. Thank you. Great. Thank you so much, Dr. Smith. I think the next question comes from Dominic Lunn from Credit Suisse. Dominic, you're next. Thanks. On the ARASENS trial in the past being the session, the data and judged by or including for the STAMPEDE trial topics instead of being signed off as the significant that- Sorry to interrupt. You're very hard to understand, Dominic. You're fading in and out. I don't know what kind of mic you're using. I don't know if anybody understood that, but I couldn't. I didn't understand. I' ll let you [inaudible]. Okay. Let's wait for Dominic Lunn to dial in here again. Let's take the next question from Sachin. Sachin Jain from Bank of America. Sachin, you're next. Sorry. I have two. I'm Sachin Jain. Sorry, I forgot to unmute myself. Two questions here for Robert, if I may. Firstly, just in the ARAMIS setting. Right. You're three years into launch. Why don't you just give a bit of color as to the share you've got to the existing agents and how you expect progression of the strong launch you've referenced, the EUR 220 million towards the EUR 1 billion to progress, and what the sort of barriers you've seen to adoption in the ARAMIS setting are. I'm relating that question to ARASENS. Would you expect the launch in the ARASENS setting to be quicker given you're the only data set of this triple with the compelling data set you've seen? What are the challenges that the doctor speaks to suggest to us that this should also be a slower launch that builds over time? Thank you. Thank you, Sachin, for that question. I think there's a couple of different dynamics playing in the marketplace now, as I stated in my opening remarks. As you will recall, the launch of Nubeqa, the initial launch of Nubeqa was happened right in the middle of the pandemic. Our representatives, for the most part, was not able to get out and have the number of you know, face-to-face type of customer interactions. We relied a lot on peer-to-peer type of discussions and digital type of outreaches to reach the different customers, et cetera. I think as the pandemic begins to wane, and our representatives are able to get out to start having more face-to-face calls and really explain the benefits of the compounds, and doctors begin to see it, I think you'll see. 'Cause we see this when we talk to physicians that utilize the compound. They really do become adopters of the compound once they use it, just you know, a few times. I think on the market share question, that is a very difficult question to get at, because the data is not always as clear-cut as one will see across the different markets, because of the. As Dr. Smith was saying, I mean, it's like the disease itself is almost like a continuation. It is a continuation in prostate cancer, so it's really hard to have market-level segmentation of the data as you do this. But what we see is that, you know, we are continuing to trend up in the way that we look at the data, probably in the 20%-22% range or so, in this non-metastatic setting and continue to trend upwards. Now obviously, if you look at this on the total market because the other drugs have broader indications than we have at the current time, it's really hard to put that in the right context because of the really smaller segment of the non-metastatic setting. So the... Probably the biggest barrier for us is just, you know, overcoming some of the issues that most companies have to overcome when you're launching drugs in a pandemic, and finding new ways to be able to reach and ensure that you're educating on the benefits of the program. I think though, if you look at the compound itself, really the last year, you know, as you know, when you go to Europe and Japan and other areas, there's quite a long time from the actual indication to the reimbursement, and so when you look at really 2021 was the first year that we had a full year of, you know, indications plus reimbursement. It's coming in around the EUR 219 million-EUR 220 million segment. As you look at the ARASENS trial now, I think what this does is begins to build on the confidence level of the compound because now you don't have just one study, you actually have two studies. If you actually look at the two studies, they both showed a greater than 30% reduction of risk, regardless if you're in the metastatic or the non-metastatic setting. I think the studies themselves will feed off of each other, based on the totality of the data. Then you layer on top of that, regardless of which setting you were in, the tolerability profile was extremely consistent. As doctors now will have the ability to begin to use this drug in the metastatic setting, I think that they will see the true benefits of this compound as they make treatment choices and options for their patients. It's hard to say exactly what the uptake will be as we go into the marketplace, but I think Dr. Smith made a comment that you know, anybody right now who are considering chemotherapy for a patient based on this data, it would be very appropriate to immediately add darolutamide to that regimen for this metastatic hormone-sensitive indication. Great. Thank you, Robert. Does that answer your question, Sachin? Or you have a follow-up? No, it's perfect. Thank you very much. You're welcome. Dominic is back from Credit Suisse. Dominic, let's try it again. You're back. Hi. Can you hear me now? Yes. Yeah. Much better. Okay, great. On ARASENS again. In the past, there's been discussion that the benefit of this indication lies potentially more in having a complete and differentiated label to market with instead of a big incremental sales efficiency, given the fact that you're trying to bring chemo earlier into the treatment paradigm in some of the patients, I assume. But the magnitude of the benefit is quite impressive. Did this change your view on the level of adoption you expect for this regimen? And I ask because obviously you're increasing your peak sales by $ 2 billion at the same time as obviously showing the ARASENS data. But is it correct to assume that the peak is more of a general reevaluation, you know, type of all indications rather than being solely on the strength of the ARASENS data? Yeah. Dominic, thanks for that question, and indeed that's correct. As we look, you know, this second study really confirms the first study in terms of the profile of the compound. We do have three additional studies, including the ARANOTE trial that will read out as a single agent with ADT. When you look at the totality of the entire program, this is where we got to the $3 billion number. It wasn't on one specific indication. It's gonna be interesting to see as physicians you know see a patient in front of them and make treatment options on whether to use you know this triplet combination with intensified therapy or not. I think it's gonna be very independent based on the physicians, based on the patients, and you know, Dr. Smith maybe wanna comment on how he would think about when to use this more intensified therapy. We see this as not just on one indication or two indications, the $3 billion number that we put out is more on the totality of the entire program and the clinical development program that we have already put forth. Yeah, sure. Happy to further comment. You know, decades ago, this term combined androgen blockade was introduced, referring to the addition of a first-generation anti-androgen like Casodex or flutamide to standard androgen deprivation therapy with a GnRH agonist. That was never proven to be helpful, so the term got dropped. We're back to combined androgen blockade, but now with drugs that really work. Drugs really work, right? Across the entire spectrum of prostate cancer, we're seeing benefit by addition of potent AR pathway inhibitor. I think there will be this generalization. Docs are gonna choose. They're gonna intensify in the vast majority of settings where we're administering ADT. ADT isn't gonna mean just Lupron, for example, or whatever injectable drug of choice. It's gonna be that plus your AR pathway inhibitor of choice. For the reasons I described, I view this as best in class. The data from ARASENS are critically important, right? I mean, not that I ever had any doubts about the strength of the data from ARAMIS, but if there were any doubters, this data should largely silence that, right? 'Cause there's this high-risk patient population, poor prognosis, metastatic disease, and you see this very large treatment effect and consistency across all the secondary endpoints. I think there will be this, to use your term, in the question, sort of generalization across the disease states. I think that's appropriate because a lot of these labels are kind of, a bit outdated, and they're defined in that way for regulatory purposes. If we focus, say, on the term mCRPC for a moment, it doesn't mean the same thing anymore, because almost no one going forward with metastatic disease should be progressing on ADT alone. When they progress to CRPC, they will have already received an AR pathway inhibitor in addition to their injectable hormonal therapy. I think it's really gonna become an issue of intensifying systemic treatment by addition of an AR pathway inhibitor. You know, individual physicians are gonna make their choice of which agent of choice. You know, I think that this is why the combined data from ARAMIS and ARASENS are so important. Great add on. Thank you. Very helpful. Thank you so much. Yeah. We have time for, like, maybe one or two more questions, and I have one more question from Harry Sephton from Credit Suisse. Harry, you're next. Brilliant. No, thank you for taking my question. I just had one, which is a follow-up on the trajectory of your expectations to that $3 billion new guidance. Between now and your patent cliff, you will have expanded generics on the market probably about six to seven years prior to your patent cliff. I just want to understand whether you expect it could be more challenging to gain share in the new to brand market as expanded generics become available and whether you factor that into your guidance. Thank you. Yes, Harry. As we think about the genericization of some of the compounds, you know, it's really important to focus on the differentiation of the compound of Nubeqa. When you look at Nubeqa, this is the only one that's been able to show this type of data with the ARASENS trial. Keep in mind that, you know, abiraterone also went generic, and the market still continues to grow as data begins to drive the utilization of these compounds. You know, part of our value proposition, as you saw from Christian's presentation earlier, when you think about the blood-brain barrier and the clean profile of darolutamide, this actually continues to offer tolerability advantages for these patients. Also, when you look at the way that we are conducting our clinical trials, yes, there will be some genericizations that will occur towards the end of the decade. But our goal is to make sure that this compound is really differentiated based on the clinical profile, the clinical benefit to the patients, and the utilization as the market continues to change. I think Dr. Smith made a really good point about how if you even just look at the castrate-resistant space, which we're not doing studies in because that space by the time you're there, have already received an AR inhibitor. The only way we would do a study there would be in combination with maybe a new modality, for example. This market will continue to change. It will continue to these drugs will begin to be utilized in a much earlier setting. As you move these drugs into the earlier settings like we have with the BCR trial and the neoadjuvant and adjuvant trial, the profile of the compound, the tolerability of the compound really has to be somewhat pristine because these patients are asymptomatic, and we feel that we have the best-in-class tolerability profile of the agents that are currently available. Our $3 billion number that we have does include some of the changes in the marketplace, but it also includes some of the shifts in the marketplace of these drugs moving especially Nubeqa, hopefully earlier and earlier in the treatment disease. Great. Thank you so much. Thank you, Harry. One more question from Damien Conover from Morningstar. Super. Thanks for taking the question and thanks for the presentation. Super helpful. One question I had, there's a great slide nine that sort of cross trials compares, Nubeqa to some of the other key molecules in the, CRPC market. As you think about this new data in the HSPC market, how would you characterize some of the cross trial comparisons there? You know, it definitely seems to be a safety benefit, but when you look at some of the efficacy, cross-trial comparisons, how do you feel it stacks up, Nubeqa versus competitors? You know, maybe I'll ask Dr. Smith from a clinical standpoint. He is absolutely the clinical expert here. Maybe there's additional comments I would add, but maybe I'll ask Dr. Smith to take that one on. Sure. The data from ARASENS is the most compelling. The other trials that included ADT and docetaxel as standard of care were a few, ARCHES, TITAN, ENZAMET, were relatively small groups and did not report a benefit of adding their respective drugs onto ADT docetaxel. Then more recently in a subgroup analysis of the PEACE-1 trial, there was a benefit to adding Abi to ADT and docetaxel, although the hazard ratio there was, I think, 0.75, so not as favorable as in ARASENS. There's also you know, sort of smaller subgroups. I think the community was not won over by the PEACE-1 data because it really is a subset analysis within a larger trial. To answer your question, ARASENS is best in class for efficacy in this specific disease setting. Great. Thank you. Thank you so much, Dr. Smith. I think we have one last question from Marietta. Marietta, you're next. Yes, thank you very much. Just one quick question, on your confidence in the earlier settings. I absolutely hear you on safety, but just in terms of extrapolating efficacy from the more advanced settings to, adjuvant and BCR, can you just speak to your level of confidence that there will actually be a high level of efficacy and the drug will actually succeed in those earlier settings? Just because, I mean, we've had, some examples of cancer drugs that have done phenomenally well in the metastatic setting, but, failed in the adjuvant settings. You can debate whether in some cases it might have been due to the drug, in some cases it might have been due to the trial design. Just any thoughts there why maybe in prostate cancer, you know, we should look at this sort of differently, why you might have higher confidence? Thank you very much. I'll answer the first part, and I would also welcome Dr. Smith if he wants to add any additional comments. You know, Christian started the presentation, this disease, the androgen receptor is the key driver here. If you can give more intensified therapies earlier on in the disease, the hope would be to be able to provide a better clinical outcome and benefit for the patients. We've seen that now, and we continue to see that in the non-metastatic setting. The next question is, should we go earlier and then also see if we can provide the same, you know, additional benefit for patients? I think when you do that, though, the profile of the compound, again, as I stated earlier, needs to have a very good tolerability profile because nearly all of these patients will be asymptomatic, and it's extremely important that the drug doesn't add burdensome toxicities for the patients. You know, the data, you know, I can't predict the outcome, nor will I predict the outcome. When we combine the fact that we have a very good profile in our compound and the fact that the AR inhibitor is the key driver of the disease, I think it's an appropriate question to ask, can we provide better benefit for these patients in this much earlier setting? You know, and what we're doing also, as we look at some of these settings, you know, we're selecting the patients who are at high risk of progressing. We're not just going to every single patient. We're really being very mindful from a clinical standpoint to ensure that we are identifying the patients who are most at risk, that may actually progress through their disease. Anyway, so that's as we think about it, on our clinical program. Dr. Smith may have additional comments that he'd like to make, just from a broader perspective. Yes, I'll answer just from the perspective of the drug, the class of AR pathway inhibitors. I have no doubt that AR is a key driver in high-risk localized prostate cancer and in biochemical recurrence after prior local therapy. I think there's no doubt about the biology there. I also have no doubt that Nubeqa and these other drugs will work in that setting. The success or failure of a labeled indication will really be, to your point, like, dictated by whether the studies are appropriately designed. It's not whether the drugs work, it's whether they're appropriately designed. Sure. You know, my prediction is that the you know, the many well-designed studies in those earlier disease states will succeed. Very clear. Thank you. Thank you all. I think with that concludes our program for today. I would like to thank all of you for your participation, and the Bayer team hopes that you enjoyed this event and found it useful. I'd like to thank you for your continued interest and stay safe. I look forward to staying in touch. Thanks so much. Thank you.