Bayer Aktiengesellschaft (BAYN) Earnings Call Transcript & Summary

Good morning, good afternoon and good evening, everyone. Welcome back to day 2 of our Capital Markets Day. My name is Oliver Maier. I'm the Investor Relations lead at Bayer. And with me today is also, again, Ariane, our moderator, who you know from yesterday. We are back here live at the communication center in Leverkusen. Today, it's a mix between live presentations and prerecorded presentations as we wanted to give you a very balanced picture. Nevertheless, time differences and travel restrictions didn't allow for all the presentations being live. While yesterday was all about the group overall and divisional priorities for the years to come, today will all be about innovational fire in all its different facets.

A big welcome from me as well. We have the pleasure to meet yesterday also. And I'm so pleased that I get to guide you through day 2 today also. If you haven't done so yet, I would now like to encourage you to check out our virtual platform because there, you can find the agenda. You can also find all the presentations. You can exchange in our chat lounge. You can also watch the Leaps exhibition there or study any of the materials and presentations in our resource center. This is where all the videos and presentations will be available after the meeting as well.

Great. So thank you, Ariane. Same procedure as yesterday. Before we go and have a quick look at the agenda, I'd like to draw your attention to the cautionary language that is part of our safe harbor statement that was also included in all the materials distributed yesterday and is also part of the material that is available on our platform today. So how is the agenda going to look like? In the first half of today's meetings, we will do a deep dive into the R&D activities with the presentation of Christian Rommel, our new Head of R&D, who joined us from Roche, and you met Christian yesterday already. After that, we will have Robert LaCaze actually giving you a lot more insight into our oncology business and our ambitions there. And finally, we will share quite some insight into our newly established Cell and Gene Therapy business.

This will also be followed by an update on our R&D activities in the Crop Science division led by Bob Reiter, who's Head of Bayer's Corp Science R&D.

Right. And at the end, we will also have insight in our Leaps at Bayer, led -- our investment unit led by Jurgen Eckhardt, who will actually share his vision to advance potentially breakthrough technology. And I think from here, Ariane, I hand it over to you again.

Thanks so much, Oliver. Well, then, let's get started. Delivering highly innovative medicines to benefit patients' needs is at the center of what we do in research and development at pharma. With a track record in innovation, our R&D activities focus on projects with great potential in terms of improving patient well-being in therapeutic areas with a high unmet medical need. And on that note, please welcome Christian Rommel. He's Bayer's new Head of Pharma Research and Development, and he's going to share his first impressions of having joined Bayer recently. Over to you.

Thanks, Ariane. Ladies and gentlemen, welcome to today's presentation at R&D pharma. I'm Christian Rommel, and I recently joined Bayer Pharmaceuticals to lead research and development. During today's presentation, I will provide you with my first impression about the R&D organization, its focus areas and capabilities, some initial thoughts about the key pipeline projects as well as some of my priorities going forward. When the news became public that I would move on to Bayer, several people were asking me, why Bayer? Well, before making the decision to take over this new position, I obviously did my personal due diligence on Bayer's Pharma division. And let me now share with you what I found out. The R&D team has established highly regarded in respect to excellence in small molecule drug discovery. They are fully committed to develop new treatments for areas of high unmet need. This is all founded on deep science-based understanding of disease mechanisms in the therapeutic areas of our focus. Also beyond small molecules, the organization has begun to expand into new science and new modalities. In my view, especially the investment into cell and gene therapy was a bold and smart move. On the areas to be strengthened, my first impression is that despite the excellent in drug discovery, there's an opportunity to focus on direct small molecules into the innovation space of medicinal chemistry and disease biology. In addition, success of internal R&D requires external sourcing of innovation. On top, attracting, developing top scientific talent is, in my view, an area to be strengthened in certain areas as well. The expertise of a R&D pharma organization is witnessed by a strong track record of execution as well as innovation during the last decade. The business delivered really differentiated and first-in-class drugs to the benefits of patients, many patients. Just to mention a few examples here, Xarelto, an oral Factor Xa inhibitor; Xofigo, an alpha radiopharmaceutical; Adempas, a soluble granulate cyclist, sGC, modulator; and Vitrakvi, a specific treatment for NTRK gene fusion proteins in tumors. To complete this list, I would also add Nubeqa for the treatment of prostate cancer and Verquvo as a new drug for the treatment of heart failure. Based on this track record, we will continue to pursue our patient-centric approach to develop new and better medicines for the future. Aligned with our purpose, science for better life, we are focusing on areas of high unmet medical need. We are working science-based and patient-centric. Our research development activities are predicated on a deep scientific understanding of disease biology and a diverse range of modalities complemented by data generation and insight analytics. New developments, new product developments need to deliver scientific and clinical innovation and need to make an impact. We all know that incremental progress will not be rewarded and it's not on our to-do list. In order to deploy our resources efficiently with focus on therapeutic areas of high unmet medical need, these are cardiovascular diseases and oncology, which still represents the 2 biggest killers in terms of number of deaths worldwide. In addition, endocrinology, metabolic dysregulation and reproductive health, as well as adjacency like ophthalmology and rare diseases, belong to our focus areas in R&D. In my view, expertise in these disease biology and therapeutic areas need to be supported by a broad and agnostic approach to modalities applied. [ Novel track ] modalities and integrated platform are key to the state-of-the-art drug discovery. We already expanded beyond small molecules into protein therapeutics, radiotherapeutics, cell and gene as well as RNA therapies, complemented by digital technologies like large field data analytics and artificial intelligence. In essence, we are focused on diseases that matter, and we are equipped with a broad modality toolbox to drive groundbreaking science to deliver innovative and transformative treatments for patients. When looking at the R&D pipeline, several assets got my attention immediately. The area of cardiovascular diseases, these are finerenone and the Factor XI portfolio. In women's health, it is elinzanetant, a KaNDy asset. And from the mid-stage pipeline, I believe that the PTX3 receptor antagonist maybe has significant potential. I also believe that the early pipeline includes some really appealing projects, especially in the areas of oncology and in cell and gene therapy. But let's first look at finerenone. Finerenone is a nonsteroidal selective antagonist of the mineral corticoid receptor. It may become a new treatment option for chronic kidney disease, also referred to as CKD, in patients with type 2 diabetes. The impact of CKD in type 2 diabetes is far reaching. We estimate that about 145 million patients suffer from CKD. While it is critically underdiagnosed, it's a major risk factor for the development of end-stage kidney disease and for an increased mortality due to cardiovascular events. CKD progression in this type 2 diabetes is influenced by 3 major factors, hemodynamic and metabolic as well as inflammatory and fibrotic drivers. Today, physicians are fighting CKD in type 2 diabetes on multiple fronts. But even with well-controlled hemoglobin and blood pressure, many patients are still experiencing disease progression. Recognizing some advancements in the field, there are more opportunities to reduce the residual risk of end-stage kidney disease and deaths from renal disease. For these patients, unaddressed inflammation and fibrosis can lead to a variety of cellular changes that permanently alter the function of the kidney. This inflammatory and fibrotic damage is a major consequence of mineral corticoid receptor overactivation in the kidney. Finerenone is targeting this overactivation of the mineral corticoid receptor. Based on Phase II data, we initiated the largest CKD Phase III trial program in patients with type 2 diabetes, with more than 13,000 patients enrolled. The first trial, FIDELIO, comes with a composite renal endpoint, while the second trial, FIGARO, the study results revealed only infrequent discontinuation due to hyperkalemia in patients who received finerenone. This clearly differentiates finerenone from older steroidal mineral corticoid receptor antagonists, which typically showed a more pronounced impact on potassium. Based on this data, we filed for proven key markets and the FDA granted priority review, and if approved, the drug could be launched in the first markets in the second half of the CRA. We believe that the potential of phenomenon goes beyond chronic kidney disease in type 2 diabetes. Mineral corticoid receptor overactivation plays also a significant role in heart failure. Mineral corticoid receptor has demonstrated beneficial effect in the treatment of certain forms of heart failure. Based on robust Phase II data, we initiated the FINEARTS-HF study, a Phase III study to evaluate the effect of finerenone on mobility and mortality in patients suffering from heart failure with left ventricular ejection fraction of greater than or equal to 40%. Currently, there are limited options available for patients suffering from heart failure with preserved ejection fraction. Given their substantial risk for cardiovascular events, this represents a critical unmet need in cardiovascular disease. FINEARTS-HF is the first trial to investigate the use of nonsteroidal selective mineral corticoid receptor antagonist in this setting. Moving on to the field of anticoagulation, where Bayer has established itself as a global leader with Xarelto. Venous thrombosis include the deep vein thrombosis and pulmonary embolism and will affect several million people worldwide. Furthermore, arterial thrombosis, including ischemic heart disease and stroke, collectively more than 10 million deaths per year worldwide. Thrombosis is the common underlying pathology of these diseases, and anticoagulants are the mainstay to prevent and/or treat thrombosis. Over the last decade, significant progress has been achieved in anticoagulation therapy. After decades of use of heparin and vitamin K antagonist, direct thrombin inhibitors and direct Factor Xa inhibitor, the so-called NOACs, define the treatment of standard today. Currently used anticoagulant produce therapeutic antithrombotic effects, either by inhibiting from thrombin or Factor Xa or by lowering the plasma levels of the precursors of these key enzymes. However, these drugs do not distinguish between thrombin generation contributing to thrombosis and thrombin generation required for hemostasis. Thus anticoagulants increase bleeding risk. And many patients who would benefit from therapy go untreated because co-morbidities may expose them to an unacceptable risk for hemorrhage. Blood coagulation Factor XI has emerged as a promising target for new anticoagulants. As the Factor XI partially contributes to thrombin formation to a greater extent than to normal hemostasis, pharmacological inhibition of this coagulation factor may offer the possibility of anticoagulation therapies with the lower bleeding risk. Hereditary deficiencies of Factor XI is known as hemophilia C. It is generally associated with a relatively mild to moderate bleeding phenotype compared to the hemophilia A or B. In fact, Factor XI deficient in individuals rarely suffer from spontaneous bleeding. In addition, epidemiological studies suggest that Factor XI deficiency confers reduced risk of thrombotic disorders. In such studies, such epidemiological findings are supported by the fact that Factor XI gene deficient, or also called knockout mice are protected from thrombosis while [ no profound ] bleeding phenotype was observed. Supported by such lines of evidence, targeting Factor XI is expected to inhibit thrombosis, but not only depress hemostasis. Targeting Factor XI may serve as a powerful route to new anticoagulants that may be associated with less bleeding risk than the currently available treatment options. We have a broad and diverse portfolio of Factor XI inhibitors, which we currently investigate in a comprehensive Phase II study program. In collaboration with Ionis Pharmaceuticals, we are developing an antisense oligonucleotide, Factor XI LICA, to depress the biosynthesis of the Factor XI in the liver. The antisense of course uses short nucleic asset sequence, which is specifically designed to selectively hybridize as the mRNA target in the hepatocytes. This hybridization typically results in the degradation of the targeted mRNA and leads to a corresponding reduction in Factor XI plasma levels. A dose-finding study with Factor XI LICA in end-stage renal disease patients on hemodialysis is currently underway. And the second approach, we are looking at osocimab, a fully human monoclonal antibody that binds adjacent to the active side of Factor XIa and prevents it from activating Factor IX in the coagulation cascade. Phase II data confirm proof-of-concept of osocimab. Among patients undergoing knee arthroplasty, post-operative, single dose of osocimab between 0.6 and 1.8 milligram per kilogram were noninferior to enoxaparin. The preoperative 1.8 milligram per kilogram dose met the criteria for superiority compared with enoxaparin for the primary VTE outcome. Osocimab is currently investigated in a further Phase II program to assess the safety and tolerability of monthly subcutaneous administration to end-stage renal disease patients on regular hemodialysis as well. Our oral therapy is a potent, direct and reversible small molecule inhibitor of Factor XIa, showing strong antithrombotic efficacy without increasing bleeding risk. It is investigated in a broad spectrum of potential indications. We initiated a comprehensive Phase II study program called PACIFIC that we test the compound in patients with atrial fibrillation, acute ischemic stroke and in patients following an acute myocardial infarction. In total, we plan to enroll more than 4,000 patients into this program. First studies are expected to be completed later this year as well as early next year. Switching gears to women's health. Vasomotor symptoms or hot flashes and night sweats are the most commonly reported menopausal symptoms linked to declining levels of estrogen. Up to 75% of women going through menopausal transition experience these symptoms, which can impact both their work and private life and are debilitating for several years for those affected. About 16 million women in the U.S. and another 16 million in Europe suffer from such menopause symptoms. The current standard of care is hormone replacement therapy. Given its limitation in nonhormonal treatment for vasomotor symptoms would be a major advancement for women suffering from symptoms of menopause. Elinzanetant, formerly known as KaNDy NT 814, is a non-hormonal dual antagonist, of course, the neurokinin-1 and 3 receptors. Neurokinin signaling increases in response to estrogen deficiency in menopausal women and has been implicated in the etiology of hot flashes. Elinzanetant is modulating a specific group of estrogen-sensitive neurons that in menopausal women, due to the absence of estrogen, become hyperactive and consequently, disrupt the body thermoregulation. Inhibition of NK3 receptor signaling may reintroduce this hyperactivity and address this dysregulation that is driving hot flash symptoms. In addition, blockade of NK1 receptors may result in lessening of the vasodilatory response in the periphery and thereby contributing to the reducing the intensity of hot flashes. Elinzanetant demonstrated significant and rapid improvement in vasomotor symptoms in Phase II. Symptom frequency was reduced in all treatment groups. Reduction was shown as early as the first week of treatment. Improvements in hot flashes were accompanied by significant benefits on sleep, mood and parameters of menopause specific quality of life assessments. Elinzanetant was well tolerated. Most adverse events were mild or moderate, and there were no serious adverse events related to the treatment. Based on those data, those exciting data, we are planning to initiate a pivotal Phase III trial this year. Another attractive pipeline assets that caught my attention is eliapixant, a P2X3 receptor antagonist. P2X3 receptors are a family of ion channels reported that are mainly localized on a sensory nerve cells. Studies have shown that P2X3 play an important role as a natural mediator of pain and nerve hypersensitivity in peripheral pain responses, and it function as an inducer of neurogenic inflammation. Eliapixant is a potent, selective P2X3 receptor antagonist that reduces nerve fiber hypersensitivity and may have multi-indication potential. It was first identified as strategic research alliance with Evotec in connection to our joint Endometriosis Research Program. But P2X3 also seems to be involved in several other diseases characterized by painful neurogenic hypersensitivity, including refractory or unexplained chronic cough, overactive bladder and neuropathic pain. Proof of concept for eliapixant has been obtained in refractory chronic cough. This is a poorly-recognized condition causing significant morbidity. About 1% to 5% of the global population suffers from refractory or unexplained chronic cough. There are currently no approved treatments available, and off-label pharmacological treatments typically have limited efficacy and high adverse event rates. Eliapixant demonstrated a dose-dependent reduction in cough frequency of up to 25% for the 24-hours cough frequency and up to 36% for the re-cough frequency. The rate of adverse events, including taste-related effects, was low across all study participants. To fully exploit the potential -- the therapeutic potential of eliapixant, we expanded the clinical Phase II program beyond chronic cough into overactive bladder, endometriosis and neopathic pain. All these conditions have significant prevalence and only limited treatment options are available today. In my previous position, I was the Head of Oncology at Research and Early Development at Roche. Thus, it should be no surprise for you that I was particularly interested in learning more about Bayer's pipeline in oncology. At Bayer, we are mainly focused on 3 areas in oncology research. In positioning molecular oncology, we exploit the intracellular oncogenic dependency with small molecules and new modalities. Deliverables from our R&D in this area include most of our marketed products, including Nubeqa, Vitrakvi and Stivarga. In the areas of targeted radiotherapies, we are utilizing alpha particle emitting radionuclides to deliver high-energy radiation energy to selectively kill tumor cells. Xofigo or Radium 223, it's the first approved RF RA pharmaceutical. We demonstrated improved overall survival among castration-resistant prostate cancer patients with symptomatic bone metastases with mild side effects owing to its localized dose deposition. We also have unique access to tumor targeting Thorium-227 conjugates, which combine the alpha in meta Thorium-227 to an antibody to selectively deliver the radiation to the target cells. In the field of immuno-oncology, we focus on select next-generation approaches and on the development of allogenic T cell based therapies. So as you can see, an already cross-modality spectrum in our oncology research spans from small and large molecules to radio and cell therapies. Let's talk about some of the highlights of our oncology pipeline. Activating mutations of epidermal growth factor receptor, or EGFR, play a major role in the development of non-small cell lung cancer. For the majority of patients whose tumors have such mutations, tyrosine kinase inhibitors, such as gefitinib or olatinib provide significant clinical benefit. The majority of patients treated with these TKIs experienced an objective response, improve progression of free survival and improved quality of life compared to chemotherapy alone. However, approximately 2% of all adenocarcinoma cases have an in-frame insertion within exon 20 of EGFR. These tumor types are generally resistant to EGFR tyrosine kinase inhibitors. Patients with these tumors have a median progression-free survival of just 2 months with approved TKIs and of about 6 months with chemotherapy, which is currently the standard of care. Thus, a very significant unmet medical need exists for these molecular defined patients. Our small molecule EGFR exon 20 inhibitor shows activity against a broad range of exon 20 insertion mutations and demonstrated anti-tumor efficacy in preclinical tumor models. It is a highly potent compound with excellent selectivity compared to EGFR wild type, which is important for activity and differentiation. In addition, our molecule is also active on HER2 exon 20 insertion mutations, which accounts for about 2% to 3% of patients with non-small-cell lung cancer. Based on preclinical progress so far, we are planning to initiate a Phase I clinical development in the second half of the year. To secure the integrity of the genome, cells have a voiced mechanism term DNA damage response, or DDR. This mechanism detects DNA lesions, signals their presence and promotes their repair. Many cancers have a defect in DDR pathways, leading to genomic instability that can either cause or promote -- and/or promote cancer cell growth. The ATR kinase plays a central role in the DNA damage response. Many tumor cells, but not normal cells, are often relying on the ATR to survive replication stress. Thus, ATR inhibition may be a promising therapeutic strategy to inhibit tumor cell growth and viability. It may also have a synergistical antitumor effect on cell lines with specific genetic alterations. Genome wide studies identified a number of genes with synthetic lethal relationship with ATR inhibition. It is suggested that increased replication stress and impaired DNA repair may increase sensitivity of tumor cells to ATR inhibition, which opens up a strategy for combination therapy. These findings may also have the potential to provide new genetic biomarkers for specific patient enrichment in clinical studies. And our ATR inhibitor demonstrates strong single-agent activity in differentiated -- in different preclinical tumor models with DDR defects. We are now investigating this novel, selective inhibitor in a Phase I program in several advanced cancer types. It is applied as a single agent or in combination with pembrolizumab, a PD-1 checkpoint inhibitor, or with niraparib, a PARP inhibitor. Study completion is currently expected for the 2023/2024 time frame. Radiation therapy is one of the mainstays in cancer therapy. We at Bayer, we are at the forefront of targeted radiation therapy, which delivers systemic radiation selectively to the cancer cells. As said before, Xofigo was the first ever approved alpha radiopharmaceutical. The physical chemical properties of the radionuclide in Xofigo mimic source of calcium. As a consequence, the radium is accumulated in the bone tissue. Based on this tissue specificity, Xofigo is used for the treatment of bone metastases in patients suffering from advanced metastatic castration-resistant prostate cancer. Xofigo was approved for this indication based on Phase III data demonstrating a significant prolongation of overall survival. Apart from Xofigo, we are now pursuing targeted alpha therapies with potential across several tumor types. Thorium-227 is an alpha radiator as well. Due to its chemical properties, it can be complex to a variety of antibodies, which we help directing the alpha radiation to the target tumor cells. We are investigating volume conjugates in Phase I in combination with antibodies targeting PCMA in prostate cancer patients and HER2 targeting radio conjugates in HER2-expressing breast cancer, gastric and gastroesophageal cancer. We expect first trial completion in the 2023/2024 time frame. In accordance with our overall cell and gene therapy strategy, we are expanding our science, our modalities in oncology into cell therapies as well. Chimeric antigen receptor engineered T cells or CAR-T cells have yielded significant efficacy in certain B-cell malignancies. Based on the success, CAR-T cell therapy is now being investigated in several hematologic and solid tumor types as well. CAR-T cells are generated by removing T cells from the patient's blood, are engineered the cells to express chimeric antigen receptor, which reprograms the T cells to target the tumor cells. The engineered T cells are propagated and infused back into the patient. This autologous approach is complex, time consuming and patient specific. The development of antigenic, donor-independent CAR-T cells is anticipated to overcome some of these technical and logistical challenges associated with autonomous CAR-T cells. This is why and where we collaborate with Atara Biotherapeutics. Atara allogeneic T cells originating from donors are generated from immune cells that have not been exposed to patients' conditions that may impair cell quality. These cells are engineered, manufactured and stored in inventory with the goal of being readily available for patients with serious diseases. Collaboration includes development candidate ATA3271, an arm next-generation allogeneic T-cell immunotherapy and an autologous version, ATA2271 for the treatment of high mesothelin-expressing tumors, such as malignant plural mesothelioma and non-small cell lung cancer. The allogenic candidate leverages Atara's novel proprietary abstain biovirus EBV, T cell platform combined with next-generation CAR-T technologies to improve efficacy, persistency, safety and durability of response. ATA3271, the allogenic version of this CAR-T, is currently in IND-enabling studies. ATA 2271, the autologous version, has enrolled in the first patient in an open-label single-arm Phase I clinical study in patients with malignant pleural mesothelioma in November 2020. I appreciate your attention to my update on R&D. Having talked now about some of the most attractive, exciting pipeline projects, you may ask what's on my agenda for the next months to come. Obviously, after being with the company for about 6 weeks, I will not be able to provide you a full picture today. But I set myself a number of key priorities that I would like to share with you today as well. First, I will learn more about the individual R&D projects and will perform a holistic portfolio review to prioritize the most promising assets. I will advance the late-stage pipeline to make these innovations available to patients as quickly as possible. I will have a look at our resources and resource allocation and how we may shift [ thesis ] resources sufficiently to fund the most promising internal or external opportunities. I will continue to enhance our focus on external innovation and plan to further strengthen access to new science, technologies and modalities. And I will continue to grow scientific talent and leadership within my organization. This concludes my presentation for today. I'm looking forward to being in contact with you in the future. I'm happy to take your questions later in the Q&A session. Thank you very much.

Christian, thank you so much for those truly meaningful insights today. If you have any questions for Christian, we are going to have a 30-minute Q&A later today. If you send your questions through the chat, I will ask those questions on your behalf in the Q&A session later on. Now let's have a closer look at Bayer's oncology business, which is, of course, one of the growth pillars of biopharmaceuticals. Robert LaCaze, Head of Oncology at pharmaceuticals will provide details on Bayer's strategy and ambition in this field, and his focus will be on Nubeqa and Vitrakvi. Now as Robert is in the U.S., unfortunately, he was not able to travel here to be with us today in person due to the COVID-19 travel restrictions. So instead, we have prerecorded his presentation for you.

Hello, my name is Robert LaCaze, and I'm Head of Oncology here at Bayer. I'm pleased to share with you an update of our overall oncology strategy as well as our recent oncology product launches. In the past 5 years, significant progress has been made at Bayer in oncology. We've been able to double the number of marketed products from 3 to 6 with multiple global approvals across a number of tumors. We've also broadened our innovative approach with precision oncology, including the launch of Vitrakvi, the first drug to ever receive an initial tumor-agnostic approval in the EU, including both adults and pediatric patients. Additionally, we have expanded our footprint in the prostate cancer marketplace with the introduction of Nubeqa for men battling non-metastatic castrate-resistant prostate cancer. And finally, we're making investments in the next wave of immuno-oncology treatments targeting cell therapy approaches. It's our goal to make oncology a future growth driver for Bayer pharma. As we view the global oncology market, it's no surprise that the modalities that are the key growth drivers will remain to be the targeted therapies and immuno-oncology. However, we do see other modalities such as radiopharmaceuticals, and they will begin to contribute to the growth of the overall market as well. Our growth strategy in oncology is based on 3 important components: one, ensuring good launches or our most recent launch brands, Nubeqa and Vitrakvi; two, continue to drive growth of our in-line brands, specifically brands like Stivarga that have potentially an upside potential with life cycle management opportunities; and lastly, focus on 3 research platforms, which are precision molecular oncology, radiopharmaceuticals with a focus on targeted alpha radiation therapies, and developing the next wave of innovation in immuno-oncology therapies. While our R&D activities in oncology are covered in Christian Rommel's presentation, let me just give you a few more specific examples of our focus. We're targeting specifically to expand our presence in select areas of oncology where one blockbuster can build a franchise, for example, prostate cancer. Nubeqa has an unsurpassed clinical profile that we feel is best-in-class. We're also conducting multiple Phase III trials along the treatment continuum to help position Nubeqa as the foundational drug for the treatment of prostate cancer. Additionally, Xofigo was the first radiopharmaceutical to show an overall survival advantage in prostate cancer patients whose disease has metastasized to the bone. We're also conducting multiple Phase III trials with Xofigo in different areas of metastatic prostate cancer. Xofigo also serves as an area of know-how across the value chain as we develop some of our early pipeline assets like the targeted alpha therapies. These medications will be an important new modality in the treatment of cancer, offering both single agent benefits as well as a new approach to combine with current therapies like the checkpoint inhibitors. I'll speak more to Vitrakvi and Stivarga later in this presentation. However, I did want to highlight the importance of our BD&L activities that seek opportunities consistent with our internal platform strategies as well as our Leaps organization, whose investments in disruptive technologies will help ensure that we will continue to drive the next wave of innovation. Partnerships will be extremely important as we progress the next wave of immuno-oncology drugs. The addition of immune checkpoint inhibitors like the PD-1s and PD-L1s have led to major clinical advancements in the treatment of cancer. I've often been asked, can Bayer become a major oncology player without a PD-1 or PD-L1? And my answer to that is, yes, but we must understand the market and the market dynamics and be able to identify the unmet need. We use strategic approaches that are scientifically and clinically driven to combine our current assets with checkpoint inhibitors where they are approved, such as our approach in liver and gastric cancers. However, we're also developing approaches in lung cancer for about 50% of the patients who are treated with targeted therapies due to the underlying molecular diagnosis. Lastly, in tumors where checkpoint inhibitors have not shown a broad clinical benefit like prostate cancer, one of the largest tumors, we're making major investments to become leaders in that disease area. As we look at the unmet need in prostate cancer, we see that the newer second-generation ARs are moving earlier and earlier in the treatment paradigm, including nonmetastatic disease and even potentially adjuvant therapy at the time of diagnosis. Patients who have this diagnosis need treatment options that not only extend overall survival, but they need an option where the survival benefit should not be compromised with burdensome side effects. Most of the nonmetastatic castrate-resistant prostate cancer patients are asymptomatic men who are fit or are leading very active lives. Prolonged side effects can be very burdensome to disease patients, and they may actually be on these therapies for 3 or more years. Additionally, a lot of these men may be on multiple medications for noncancer reasons. So having a treatment option with limited drug-drug interactions can provide additional flexibilities for physicians treating these patients. Nubeqa is a structurally unique second-generation AR inhibitor that delivers what we call a quality of survival. What we mean by that is that Nubeqa prolongs lives without negatively impacting the everyday lives of men with non-metastatic castrate-resistant prostate cancer. In the ARAMIS trial, which was published in the New England Journal of Medicine, Nubeqa delivered an overall survival benefit with a 31% reduction in the risk of death. Furthermore, there was a 40-month metastasis-free survival benefit as well. Regarding the AE profile, the frequency was comparable to ADT alone. It was observed that Nubeqa's tolerability profile remained this way even with longer follow-up. This is particularly important for key adverse events that really matter to patients, such as mental impairment, fractures, falls and hypertension. In fact, fatigue was the only adverse event that was greater than 10%, with a rate of 13% versus 8% for the placebo group. What this means is that patients are able to stay on full doses of therapy for longer, as shown by the discontinuation rates of the adverse events of Nubeqa being no different than to placebo. Lastly, Nubeqa had a favorable drug-drug interaction profile, which again is particularly important for this patient population. All of these key attributes and benefits combine to make Nubeqa a very attractive treatment option for these patients. To date, we've seen a strong Nubeqa launch performance with rapid approvals of our regulatory bodies and rapid assessment by payers. As a reminder, when we look at Nubeqa's launch performance, we only look at the non-metastatic castrate-resistant prostate cancer market indication for which it's actually approved. This is a much smaller market than the metastatic disease market. And while it's not easy to launch a new brand in the middle of a global pandemic, and despite having limited face-to-face calls with physicians by our field teams, we are seeing market share gains in the non-metastatic castrate-resistant prostate cancer area, with continued month-over-month growth of new prescribers and good recognition of a differentiated profile with positive repeat subscribers. And we're still in the early phases of a global launch with 2020 seeing approvals in about 44 countries, and 26 of those countries have submitted for pricing and reimbursement. External validation of the differentiated profile can be seen by the recently granted accelerated review and approval of Nubeqa in China despite not having local patients being enrolled in the ARAMIS trial. Additional validation comes in Germany where Nubeqa was the only second-generation AR inhibitor to be awarded an HT assessment of a considerable benefit rating by IQWiG and the GBA. This rating is very difficult to achieve and highlights the importance of not only the clinical benefit, but also the favorable adverse event profile of Nubeqa. As mentioned earlier, we are focused at Bayer on becoming a global leader in prostate cancer. We believe that the highly differentiated product profile of Nubeqa will make it a great foundational product to build our leadership vision. Hence, we are conducting multiple Phase III trials across the treatment continuum of prostate cancer from the adjuvant setting all the way to the metastatic setting with or without chemotherapy. In addition, we're conducting an additional Phase III trials with Xofigo in men with castrate-resistant prostate cancer that has metastasized to the bone, again, with or without chemotherapy. And we continue to partner with the prostate cancer community to ensure that we understand the needs and to deliver the important therapeutic options that can be the cornerstone of care. One of our key platforms at Bayer is identifying and developing molecular targeted cancer drugs as part of our precision oncology strategy. Vitrakvi is our first drug to be approved with a companion diagnostic. However, Vitrakvi is also the first drug in the industry to be approved in the U.S. and the EU with a tumor-agnostic indication for both adult and pediatric patients as an initial indication. Vitrakvi treats a rare form of cancer called TRK fusion cancers. TRK fusion cancers are present in less than 1% of the overall cancer population. So the challenge is to find and identify these patients. However, when the appropriate patient is treated with Vitrakvi, the results are usually very impressive. This slide demonstrates the response of TRK fusion cancers through Vitrakvi. The response rate occurs across all tumor types with an impressive response rate of 71% in adults and over 90% in children as well as in primary CNS tumors and tumors with CNS metastases. However, what's even more impressive is that 2/3 of the responders are still in response after 2 years of treatment with an impressive 36.8 months of medium progression-free survival. And lastly, Vitrakvi was well tolerated, with less than a 2% discontinuation rate due to drug and adverse events. To date, over 1,000 patients have been treated with Vitrakvi and we maintained our peak sales potential of greater than EUR 750 million. Currently, Vitrakvi has gained regulatory approvals in 42 countries with additional launches expected in 2021. The largest single hurdle to [ use so ] is testing and finding the patients. Estimated testing rates have increased since we first launched the brand in 2018 from about 24% to 35% in 2020 in the U.S. and from about 28% to 36% in Germany. As more and more patients benefit from comprehensive genomic testing, we anticipate that testing rates will continue to increase. We are also working with different diagnostic companies to develop and deliver quality tests to accelerate testing. Vitrakvi is an exquisite example of innovation and is at the leading edge of precision medicine. So as the market continues to move towards precision medicine, Vitrakvi is well positioned to offer unprecedented clinical benefit to TRK fusion patients. Another important element of our overall strategy is to drive growth of our in-line brands. Stivarga has seen 2 consecutive years of greater than 15% year-over-year growth and achieved 2020 global sales of EUR 475 million. Stivarga showed growth in 2020 across all markets. One of our overall pharma strategies is growth in China. Stivarga was launched in 2018 in China, and by 2020, had achieved approximately EUR 100 million of annualized sales. Globally, Stivarga will continue to grow in the near future and has the potential to become a blockbuster brand. Stivarga currently has 3 indications: second line HCC, third line colorectal and third-line GIST. Stivarga has shown potentially exciting benefits in IO combinations, as noted in this data with a PD-1 inhibitor in gastric cancer. This data will be confirmed in our Phase III trial. In areas of very high unmet medical needs, such as glioblastoma, promise in Phase II data has also been reported with Stivarga, again, which we are confirming in a Phase III trial. In addition, there are Phase II studies underway across multiple tumors with PD-L1 inhibitors. The plan is to continue to invest in Stivarga as a growth brand to ensure we realize its full potential for both patients and for Bayer. In summary, significant progress has been made in Bayer oncology in the past 5 years. Oncology is now poised to play a major role in the transformation of pharma's overall business. We have a near-term strategy of maximizing our in-line and launch brands with a specific focus in the prostate cancer market and Nubeqa while at the same time, investing strategically in focused R&D platforms, including molecular targeted approaches, radiopharmaceuticals, specifically, alpha radiotherapies, and partnerships to develop the next generation of IO approaches, including cell therapies. External integration with BD&L and R&D partnerships will play a vital role in our pipeline growth, which should lead Bayer to becoming a future leader in key segments of the oncology market.

I want to extend my thanks here also to Robert. And if you have any questions for him, he will join us virtually later for the Q&A session. So input your questions, and I will ask them on your behalf later on. Next, after a short 5-minute break, we're going to share some insight into Bayer's new Cell and Gene Therapy Platform. So stick around. [Break]

Welcome back. Cell and gene therapies are an emerging and exciting field that has the potential to revolutionize innovation in the pharmaceuticals industry. And Bayer wants to be at the forefront of cell and gene therapies, implementing a comprehensive strategy for the last year. Now I want to welcome Wolfram Carius. He's Head of the newly established Cell and Gene Therapy unit at pharma. And he's going to be joined by Emile Nuwaysir, President and CEO of BlueRock, as well as Sheila Mikhail, co-founder and CEO of AskBio. And they're going to share their insights with us into their pioneering work to bring breakthrough therapies to patients. Now once again, due to the COVID-19 related travel restrictions, all 3 of them were not able to join us today. So they have prerecorded their presentations for you. Let's take a look.

Ladies and gentlemen, it's a great pleasure for me to introduce you to Bayer's new activities in cell and gene therapies, an emerging and exciting field that has the potential to revolutionize innovation in the pharmaceutical industry. I'm Wolfram Carius, and I am the head of the newly established Cell and Gene Therapy unit at Bayer's Pharmaceuticals Division. This unit steers our strategy in the area and orchestrates all activities along the value chain, providing an innovative ecosystem for all involved. This unit steers our strategy in the area and orchestrates all activities along the value chain, providing an innovative ecosystem for all involved. Through this strategic platform, we further consolidate and strengthen our emerging leadership in this field and we have taken a transformative step to deliver breakthrough innovation to patients. But why investing in cell and gene therapies? Cell and gene therapies offer, for the first time, the possibility to address the root cause of disease. It may provide options for conditions considered intractable or where the current standard of care is insufficient. Cell and gene therapies employ disease intervention mechanisms distinct from traditional treatments. Therefore, it's -- they offer curative and regenerative treatments by, for example, replacing a faulty gene in the right tissue. Based on early evidence, we believe cell and gene therapies will dramatically alter the standard of care across multiple conditions to the benefit of the patients. Bayer wants to be at the forefront of cell and gene therapy. And to achieve this, we are strengthening our internal capabilities, while pursuing external strategic collaborations as well as acquisitions and licensing. These investments are carefully curated and selected to establish a synergistic platform. Strategically, we are focusing on selected areas such as gene augmentation, gene editing, stem cell therapies and allogeneic cell therapies. During the past month, we have made tremendous progress to set up our Cell & Gene Therapy Unit. The acquisition of AskBio last year created the basis for our gene augmentation program. AskBio now represents one of the most advanced and industry-leading AAV vector gene augmentation platform. It already has demonstrated commercial applicability across different therapeutic areas. This acquisition also comprises integrated manufacturing capabilities and capacities, including an established contract development and manufacturing organization called Viralgen which already generates revenues today. Sheila, the CEO of AskBio, will tell you more about the great achievements that have already been made. With the acquisition of BlueRock in 2019, we built a leading position in cell therapies. BlueRock is a company focused on development of engineered cell therapies. It is a fundamental element of our strategy in the area of allogeneic cell therapies. While gene editing is today the essential cross-platform enabling technology for most gene and cell therapies, we further develop our CRISPR-Cas technologies with the ambition to be at the forefront of in vivo gene editing. But why don't we let our partners at AskBio and BlueRock speak for themselves? With great pleasure, I'd like to introduce to you Sheila from AskBio and Emile from BlueRock. Sheila will talk about her achievements at AskBio and Emile will speak about BlueRock's approach for potential treatment of Parkinson's.

AskBio is a gene therapy company. We develop drugs for devastating disease. Often, traditional methods of developing drugs have not yielded viable therapeutics for the diseases we are tackling. We represent over 350 professionals working in 5 different countries. There are 3 different components to our business. First, therapeutics; second, contract manufacturing; and third, IP monetization. Dr. Richard Jude Samulski and Dr. Kathy High lead our Therapeutics business. Dr. Samulski was the first to clone AAV for therapeutic purposes. He is largely known as the father of the field. Dr. Kathy High is the founder of Spark Therapeutics. There, she brought the first FDA-approved drug using AAV to the market. Our second business, the contract manufacturing business, is comprised of 2 different subcomponents. First, we operate underneath the trade name Viralgen for the production of GMP virus for the industry. We use our Pro10 cell line, which is the highest yielding cell line, for that purpose. Our second segment is operating under the trade name Touchlight AAV. It produces an alternative to plasma DNA for the beginning starting materials of AAV virus manufacturing. Our alternative method is called Doggybone DNA. The third business is IP monetization. We do not use our IP in the development of our own drugs; we out-license it to others and generate milestones and royalties. We have spun out several companies using our IP. First, we spun out Chatham Therapeutics for the development of hemophilia drugs using our IP. Chatham was sold to Baxter, now Takeda, in 2014. Second, we spun out Bamboo Therapeutics to use our IP for the development of a drug for Duchenne muscular dystrophy. Pfizer bought Bamboo in 2016. Every approved AAV therapeutic on the market today uses our technology. We generate milestones and royalties from the out-licensing activities. Gene therapy attempts to fix disease at the root cause. If you have a genetic defect, that means that you have a gene that is not properly functioning. What gene therapy does is it puts a good gene into the body to do the work that the defective one could not do. You may ask how do we do this. Well, all of us are familiar with COVID. And we now know that viruses are very good at infecting cells. What we do is we take a nonpathogenic virus, called adeno-associated virus, AAV, and we take out the wild-type DNA of the virus. This leaves the protein shell. Into that protein shell, we can put a normal gene. We can use the shell then to infect our cells of interest. Typically, we can deliver it with an IV injection. Once it gets into the body, it goes to the cell, where it uses the cell's machinery to pump out the protein of interest. We have the potential to do that with just a onetime treatment. And the effects are expected to be sustained, potentially lifelong. There are several benefits to the AAV system over other vector systems. First, it produces high yields. So that means it's relatively easy to manufacture. Second, it has a very mild immune response, meaning that it doesn't really create much immunogenicity when we deliver the therapeutics. Third, we can target a wide variety of cell types, and that gives us the ability to develop drugs for multiple different diseases. Fourth, it has a very good safety record. It's been in the clinic many times and has established its safety. And fifth, it can be used for gene editing purposes as well as gene augmentation. We have created a large toolbox of novel AAV technologies. This toolbox enables us to create an infinite number of AAV therapeutics. Our toolbox consists of technologies that are the best-in-class capsids and promoters. Capsids are the delivery system that gets our AAV therapeutics to the target cells. We have the ability to target specific cells, de-target other cells and minimize the effects of pre-existing neutralizing antibodies. With respect to the promoters, our promoters increase the potency of our AAV therapeutics and avoid off-target expression consequences. We also have promoters that can turn on and off transgene expression and can rheostat up or down the amount of therapeutic that is given. We have one of the best-in-class manufacturing processes to support the development of our AAV therapeutics using our novel technologies. The Pro10 system is the foundation for our manufacturing processes. It is a HEK 293 cell suspension system. It has one of the highest yields in the industry for a producer cell line. We're also fully backward integrated into plasmid production, but we don't make traditional plasmid DNA. Instead, we innovated and create a newer type of production called Doggybone DNA. Doggybone DNA has several advantages relative to plasmid DNA. First, it is a much faster cycle time. Second, its costs are much slower. And third, it has the potential to have a safer product because we avoid E. coli and fermentation processes. There are over 800 patents that support our novel toolbox. As you can see from our pipeline chart, we are developing AAV therapeutics for both rare monogenetic diseases as well as pathway diseases. We are currently in the clinic for Pompe, congestive heart failure, Parkinson's and multiple systems atrophy. Within the next 12 to 18 months, we will also be in the clinic for limb-girdle 2I, MMA and Huntington's disease. We have several other projects in earlier stages of development, including for Angelman's disease. Fourth, we needed to combine our technology with the best-in-class medicinal chemist. Bayer has the best compound library. They also have world-class medicinal chemists. We know that with the use of small molecules, we can increase the potency of our AAV delivery systems. We can also use small molecules to turn on and off transgene expression. We want to stay focused on what we do best, AAV drug development. Therefore, it was essential that we partner with a big pharma that had extensive distribution channels. We will use Bayer's distribution channels to distribute our products on a global basis to all patients who need them. I'd now like to turn it over to Emile Nuwaysir.

Thank you, Sheila. Our mission at BlueRock is to develop authentic cellular medicines to reverse devastating diseases. And we've chosen this mission because there are hundreds of millions of people worldwide today that suffer from degenerative conditions for which medicine really has no answer. As an example, there are 34 million heart failure patients who suffer today; 8 million people who suffer from Parkinson's disease. And for those 42 million people, the best that we can do with medicine today is manage their symptoms and hope to slow their decline. Why is that? Why is it that these diseases are so difficult to treat? It's because these diseases and many others like them have a terrible common root. And that root is the degeneration of the tissue and the loss of the healthy cell. And once that cell is lost, these incredibly powerful medicines that we think of today, drugs, devices, surgeries, they don't work well. When the tissue is degenerate, these medicines don't work well. We need a new answer, something that addresses the degeneration itself, that has the potential to reverse the disease. And at BlueRock, we think we have that answer. We're developing a novel approach we call cell+gene, which allows us to manufacture authentic human cells and to replace them in the body. And by replacing them, we can restore the function that is missing and reverse the degenerative condition and reverse the disease. We call this authentic cell replacement. But because these cells are manufactured, we can engineer them for enhanced efficacy and safety and to carry payload into the tissue. And this payload, we believe, could be very powerful to treat rare and chronic disorders. And we call that engineered authentic cells. We're focused today in 3 therapeutic areas: cardiology, neurology and immunology. And I'll explain our lead program and some of our other programs in a moment. This is all based on foundational science, the subject of the 2012 Nobel Prize, called an induced pluripotent stem cell. What we do is we take a normal blood draw from a consenting adult and in a onetime process, convert the blood cells in that sample to a pluripotent stem cell, an induced pluripotent stem cell. And that cell has 2 very powerful properties that make it the ideal basis for a medicine. That is, it will double every day. If you put it under industrial control, it can double every day. It also has the potential to turn into any cell type in the human body. And when you combine those 2 things under industrial control, you have a very powerful manufacturing platform. You can also combine this with CRISPR-Cas genome engineering, the subject of the 2020 Nobel Prize, and this allows you to engineer the cells so that they carry enhanced function, efficacy and safety. For example, engineering for self, so that they are not rejected by the patient; or engineering to carry additional functions, what we call payload. And examples of this would be the midbrain dopaminergic neuron that we're developing to treat Parkinson's disease; or a microglia cell, which is your brain's primary immune cell, and engineering that so that it can carry enzymes and payload into the brain. Those are 2 examples, real-life examples of things we're developing at BlueRock. We applied this platform to a very broad number of potential indications, you can see listed on the slide here, in neurology, immunology and cardiology. In neurology, we have 4 programs in: oligodendrocytes, which are a supporting cell of the brain for demyelinating disorders; the dopaminergic neurons, I'll tell you about in a moment, to treat Parkinson's disease; microglia, that could broadly be used to treat neurodegenerative conditions; enteric neurons to treat Hirschsprung's disease. Specifically, our lead program is Parkinson's. You may know Parkinson's is the second most common neurodegenerative disorder worldwide today. It affects almost 8 million people. It is a crushing and debilitating disorder that's progressive and today, it is irreversible. And it leads to a loss of motor control so that simple things like swallowing become impossible. If you've seen it up close, you'll want to do something about it. Our founder, Lorenz Studer, in 2010 and 2011 published seminal research papers where he showed how to turn a pluripotent stem cell into that authentic midbrain dopaminergic neuron that is lost first in Parkinson's. In the middle of your brain, the healthy adult has several hundred thousand of, a tiny number, of these cells, about the size of a half a grain of rice in your midbrain, and that controls your motor function, the connection between thought and action. He demonstrated how you could turn a pluripotent stem cell into this exquisite and rare cell. And he showed for the first time that it had all the functions that were needed. And when you put it into an animal model, it reversed the symptoms of Parkinson's in that animal model. We have done similar studies. We've industrialized the manufacture of that cell, done the careful safety and efficacy studies, prepared and filed with the FDA and we're entering a clinical trial to test that cell in Parkinson's patients. That trial will initiate this quarter. It will be for an open-label trial, where the goal is safety and tolerability, but it is in Parkinson's patients where we hope to see some therapeutic benefit. There's 10 subjects, patients that are between 5 and 15 years of diagnosis in Parkinson's who do respond to L-dopa, but are inadequately managed and they get inadequate relief from that drug. We expect over the next 1 to 2 years to see the safety and hopefully, the efficacy from that study as we enroll patients. I'm very happy and pleased to tell you the story today and be part of BlueRock. We're incredibly excited about what we're doing and to be part of Bayer. And with that, I'll turn it back to Wolfram Carius.

I hope that you share our excitement about the future we see for our engagement in cell and gene therapy. As Sheila and Emile outlined, our approach in building this unit is somewhat different from most of our competitors. Our operating model for cell and gene therapies leaves partners operate autonomously and fully accountable to develop and progress their portfolio and technology. In fact, this should enable our partners to realize the benefits that can come from being part of a larger organization to get the best of both worlds. In our view, this is essential for preserving the entrepreneurial culture and positions Bayer as a partner of choice. And this effort is already bearing fruit. Our development portfolio of cell and gene therapies comprises already 6 clinical assets. Leading programs includes Pompe disease, Parkinson's disease, hemophilia A and congestive heart failure. With over 15 preclinical assets in the cell and gene therapy field as of today, the pipeline is expected to grow steadily year by year, too. We have made bold steps to expand into cell and gene therapy. And we are convinced that this technology will revolutionize the way we may treat or even cure diseases that are not addressable today. Bayer has laid the foundation to be a leader in this critical endeavor. Thank you.

Well, thank you so much for sharing those phenomenal insights on how you're bringing breakthrough therapies to patients. And if you have any questions, don't forget to put them into the chat, and I will ask them on your behalf in the 30-minute Q&A session we're having later on. So in the first half of today's Capital Markets Day, we, of course, dug deeper into some of the future growth drivers for our Pharmaceuticals Division, but now we're going to switch gears and we're going to set our focus on research and development in Crop Science. Stay tuned for that. [Presentation]

Nice to have you back. Bayer's Crop Science business continues to lead the agricultural sector with unmatched R&D investment. Discovering and developing new seed and trait technologies, chemical and digital tools are helping us shape the future of agriculture. Please welcome now Bob Reiter, Bayer's Head of Crop Science R&D. And he's going to share with you an update on our R&D activities at our Crop Science Division. Over to you.

Good afternoon and welcome. It's a pleasure to be with you today. I'm Bob Reiter and I lead our global R&D for the Crop Science Division. This annual update on our research in Crop Science is something we always look forward to because it gives us the opportunity to share with you all the exciting advancements we've made in seeds and traits, crop protection and digital tools. Our mission is to shape agriculture to benefit farmers, consumers and our planet. And because of our leading position in those areas, we're doing just that. That's important because despite how commodity prices ebb and flow, in any given year, as we look to the future, we see an attractive and growing ag input market that is fueled by multiple mega-trends. When coupled with climate-driven harvest losses and increasing sustainability awareness, this means we have to innovate to produce more with less. So when my team goes to go work every day, we're laser-focused on working against that goal. To do so, the priorities for my organization are to first pursue sustainable innovation and deliver the leading R&D pipeline of crop projects. Next, to develop next-generation biotechnology traits and optimize our germplasm library with advanced breeding technologies. At the same time, advance new small molecules and biologicals. And finally, unlock the opportunity for new business models with data science. As you heard from Liam yesterday, we are the leader in sales and profitability and we're matching that with the leading investment in R&D that is roughly twice the size of our peers. These resources are more than financial. With approximately 7,100 R&D employees in more than 50 countries, we serve as the technology provider to the industry and are the partner of choice for new technologies. We know that we need to take advantage of the great science that happens inside and outside. Our open innovation model is designed to ensure that we have access to the best that science can offer. And we've got a broad network that supplements the great work our discovery teams are leading. Our agreements are centered on advancing solutions in key areas, which includes sustainable protein, transformational technology, sustainable ag services and inputs and helping farmers control threats to their crop productivity and breakthrough biology. These agreements take on many forms, including new companies funded by Leaps like Joyn Bio and its work to engineer nitrogen-fixing microbes for corn or licensing deals we signed to access new technologies. This network, combined with our in-house capabilities, as outlined on Slide 6, helps us to unlock new potential in breeding, biotechnology, small molecule development, biologicals and data science. And we've assembled the world's premier innovation platforms in agriculture and our strength and scale in each of these 5 scientific disciplines gives us significant competitive advantage in creating the solutions for growers that will meet the challenges they face today and tomorrow, whether it's the 1.5 billion data points generated by Precision Genomics to deliver biotech traits and accelerate genetic gain, or the 30 to 60 molecules selected for testing annually in our small molecule program. In addition to screening hundreds of thousands of microbes every year, we're also the partner of choice for chemical and biological seed treatments because of our leading seed and trait footprint. To that end, we delivered more than 20 key products and formulation advancements in 2020 and commercialized more than 430 new hybrids and varieties across corn, soybeans, cotton and vegetables. These projects generate real value. We're expecting nearly EUR 30 billion in non risk-adjusted peak sales for the products we're developing. Roughly half of this peak sales figure is expected incremental sales and the rest are replacement sales that sustain our base. These annual advancements and the continual progress my team is making is expected to keep our pipeline full for the next decade and beyond. Slide 8 does a great job of summarizing the balance across the reporting segments and the value that we expect to be created from our investment every year. We also listened to you and have aligned our pipeline values by our strategic business reporting entities in our appendix to make your business modeling easier. Let's move to biotechnology next, where Bayer remains the world's foremost developer of biotech traits. We've built upon decades of experience now in the field, from our best-in-class screening capabilities to the world's largest field testing footprint, to our unrivaled regulatory experience. In many cases, we've now moved on to our fifth generation of improvement for insect control and herbicide tolerance. Let's take a closer look at an example, starting first with our soybean portfolio on Slide 11. Liam spent a bit of time yesterday talking about XtendFlex soybeans. And following shortly behind and expected in mid decade, we have HT4, the industry's first 5-way stack of herbicide tolerance coming in soybeans. This Phase III trait offering adds another 2 modes of action, tolerance to HPPD and our own proprietary 2,4-D tolerance. The efficacy and weed control flexibility that we expect this product to deliver is very exciting. And you can see how well the tolerance is expressed in the plant in the photograph on the left, taken at a demonstration plot in Illinois this past summer. But we aren't stopping there. In Phase 2 of our pipeline, we are adding PPO tolerance. Ultimately, what these technologies will offer our farmer customers is flexibility. They will be able to choose the weed control options that suit their operations best, knowing that the varieties they've chosen offer premium genetics and the ability to manage weeds very well on the farm. Moving to South America. Insect control in soybeans continues to be a key growth driver for us. The Intacta franchise is well-established in the region and all regulatory approvals have now been secured for Intacta 2 Xtend, with an expected launch expected later this year in Brazil. However, the next generation is what we are focused on now and a new technology is already in Phase III. It further enhances the insect control spectrum that the Intacta franchise offers by delivering multiple modes of action for insect control. We believe that the current acre opportunity for this third-generation offering has a fit across South America, with, of course, a focus on Brazil. Sticking with varietal row crops, I wanted to highlight a very important introduction for cotton growers called ThryvOn technology. Successive generational improvements of biotechnology traits have been a hallmark of our insect and weed control technologies for more than 10 years, but ThryvOn represents a very important first for us. This is the first biotechnology trait ever introduced for piercing and sucking insects. It fills an important need in the cotton market. And as we expect this trait to offer better control and reduce insecticide use with an acre opportunity of more than 10 million acres in the United States. Looking at this photograph, it is clear to see that plants protected with ThryvOn are producing much more cotton. It's a very impressive trait and we expect to broadly license it. Now moving on to corn on Slide 14. Our growth in this segment is supported by key launches of new insect trait offerings in corn in the next 2 years, both of which will include our new RNAi-based corn rootworm trait, the very first in the industry. Brazil and Argentina are gearing up for the launch of VTPRO4 for the 2021-2022 season as an upgrade to our current leading corn trade offering in that market, VT Triple PRO. This new stacked offering has received all the necessary regulatory approvals and includes an additional mode, above ground insect control, which is extremely important in tropical Brazil. Meanwhile, in the U.S., the new corn rootworm trait is expected to be launched in 2022 under the brand name, SmartStax PRO. For above ground control, our fourth generation of Lepidoptera protection continues to show outstanding efficacy. And like the RNAi-based corn rootworm trait, it will have a nice market fit in South America. In fact, we recently received full cultivation approval in Brazil for the technology, which marks a critical milestone for our planned commercial launch in the middle of the next decade. Staying with corn, it's worth reiterating Liam's comments yesterday around our continued excitement for short stature corn. We believe this product will transform corn production in 3 key categories, by enabling more precise use of crop protection, optimizing the use of key resources and of course, reducing crop loss. I want to stick with that last point for a moment, as short stature corn reduces crop loss resulting from green snap and stock lodging, which can happen under challenging environmental conditions like high winds. In fact, in the United States this past summer, we saw one of the most significant wind events that the Corn Belt has seen in some time. This image was taken from high above one of our test locations in Iowa in August. What you're seeing are blocks of short stature corn still standing while traditional hybrids planted in bordering rows appear feathered and are leaning over. While this was clearly a devastating event, it offered a unique opportunity for us to see how the hybrids performed in real-world conditions. Needless to say, we're excited about what we saw and the benefits this will offer to growers in the future. These traits and technologies help to protect the inherent yield potential of the seed itself, but another important engine for growth in our key crops are the new hybrids and varieties we launch every year, which sustain and improve our leading seed portfolio. To do that, we commercialize more than 430 new hybrids and varieties across corn, soybeans and vegetables annually. These hybrids and varieties perform better in growers' fields and is a key enabler of achieving price/mix lift for our sales teams. Although performance varies because there are many factors a farmer has to manage, we generally see several bushels per acre or pounds of cotton lint improvement over comparable products that the farmer can buy. To deliver those gains, it, of course, starts first with germplasm. And we've compiled the largest and most diverse collection in multiple crops, which enables billions of possible genetic combinations. And with our unique tools, we're able to generate leading products for our customers. We genotype those seeds, grow them in protected culture, test them in the field and analyze those results to help deliver ever-better products to our customers. While that process has become more efficient and more predictive over time, that evolution has accelerated and we expect to be even more transformational in the next 5 to 10 years. We're calling the next phase of our breeding effort precision breeding. And the best way to think about it is that it has evolved from selecting the best seeds to actually designing the best seeds. And the way it works is artificial intelligence selects from a nearly infinite number of potential gene combinations and then matches these precisely to customer needs. Our breeding pipeline, now globally connected, continuously learns through new data, allowing us to optimize recommendations that maximize customer experience. It's a truly remarkable transformation that has occurred. And tools like gene editing are giving us even more capabilities to refine and deliver what our customers need. Gene editing is a science you've heard us talk about for a few years now. But the possibilities in the area are really beginning to take shape. Our efforts are directed toward traits with high commercial relevance, such as disease control or making the plant more productive. In fact, together with our collaborator, Pairwise, we've now identified nearly 200 unique gene sequences that can improve productivity or disease resistance across a variety of commercially relevant row crops. For example, we've also found a unique target that results in increased kernel rows, and more rows of kernel means more yield for the farmer. It's a very exciting development in an early phase of research, but it's an excellent example of what gene editing is capable of achieving. Let's shift now from seeds to crop protection innovation that's designed to protect the genetic potential of the seed on Slide 22. You heard from Liam yesterday about the critical role that crop protection will play in the midterm growth of the company. And I'll elaborate on how efforts in my organization are contributing to that and ensuring it continues through this decade and beyond. And it starts by discovering promising candidates, which our researchers are doing at a far greater pace than in recent years. By refining our approach to early phase research, we've been able to double the number of small molecule candidates in discovery. New modes of action like these are building upon our exceptional track record of success in delivering new active ingredients to the market, just as we have in biotechnology traits. In fact, we've launched at least 1 new active ingredient every year since 2007, 15 to be exact. And we have about 10 active ingredients in the pipeline today. The strides we've made in small molecule discovery allow us to increase the number of developmental candidates with new modes of action and a higher probability of regulatory success. This stems from our extensive early safety testing and from the use of differentiating starting points in discovery, identified through complementary technologies in screening and phenotyping, all fueled by data science. That's particularly relevant because while we've been focused on discovering new molecules, we also have an equal focus on formulation innovation to maintain efficacy and extend the life of our vast portfolio. To illustrate how this works, let's look at the active in our Luna brand family of fungicides, fluopyram. We grew fluopyram sales as we expanded its formulations and registrations across crops, spectrum and application methods. This drove an eightfold increase in sales of the molecule since its initial launch. And we still see the potential to double the sales over the next decade. Our technical expertise, extremely high standards for safety and keen awareness of grower convenience and use preferences has driven our leadership in life cycle management and has defined our approach. Let's move to new actives next. With a more than EUR 300 million peak sales potential, Plenexos is the next-generation ketoenol insecticide that we're looking forward to launching in 2024. This foliar and soil-applied insecticide is very effective against key sucking pests like aphids and white flies across a broad range of row crops and horticultural uses. You can see the visible difference in the plants protected with Plenexos compared to the tattered leaf tissue of the unprotected plants. We expect to begin regulatory submissions next year and are planning to commercialize the insecticide in several world areas, including the Americas and Asia Pacific. Switching to herbicides, I'd like to provide you an update on a molecule that we debuted last year in Phase II of our R&D pipeline, and it already has advanced to Phase III. This is the first new mode of action in post emergence herbicides in more than 30 years. The reason it's so beneficial is that it offers very effective post emergence control of tough grasses that have shown resistance to glyphosate. Plus, we believe it will have many uses in various markets beyond traditional nonselective use. You could see how well this herbicide controls resistant weeds versus glyphosate alone or glyphosate with another herbicide. So we're very excited about the opportunity. Additionally, this opens opportunities for herbicide tolerance trait systems and we've already undergone some of those approaches under evaluation. Liam talked about the strategic importance of our Fox Xpro soybean fungicide formulation in Brazil. Coming right behind it in Phase IV is the next-generation Fox Supra, which includes Indiflin in the formulation. Indiflin is a new technology that is very strong against Asian soybean rust and it will be the new technological backbone of the Fox family of fungicides. Fox Supra combines Indiflin with Prothioconazole to help reduce the development of resistance and broaden the spectrum of efficacy to other relevant diseases. Finally, I'd like to close the crop protection update with an overview on our biologics platform on Slide 28. This is an area that really exemplifies what it means to be able to offer farmers tailored solutions for the challenges they face. While biotech traits and small molecules usually take more than a decade to develop, the path to market for biologics is typically shorter, only about 4 to 6 years, and we remain a key partner of choice in the area to commercialize new options. With our core competencies in fermentation, formulation, field testing and grower support, we're actively developing exciting new options for farmers as well as sustaining our leading lineup of biologics. That brings us to Serenade, which offers unique ways to address emerging soil needs and counter foliar bacterial diseases. And we're improving upon it, with a product called Serenade Soil Activ. It's basically an easier product for farmers to handle, with lower use rates than Serenade ASO, an important brand in the Serenade family. Serenade Soil Activ is launching in the U.S. and Australia this year and broader global uses will follow in the years ahead. This is 1 of 3 new products that we've added to the commercial portfolio recently, including Vanity Citrus and Flipper, a biological insecticide for use in horticultural crops. We've covered a lot of ground and talked primarily about individual projects that we plan to sell in the years ahead. However, unlocking the true value of these products is further informed and enhanced through data science. Today, farmers are on using 50 -- FieldView on more than 150 million subscribed acres around the world. The connectivity from those acres, logging information from planters, sprayers and combines, generates valuable data. More data translates into better models, which leads to improved recommendations for growers. This improves with each season as we get new data. Today, we're taking that a step further by integrating customer data into our R&D process. This creates a more informed pipeline, which is better aligned with our customers' needs. So how can better data help us conduct better research and help our customers farm differently? Well, we know that farm productivity is significantly influenced by seed and trait selection. And then after that seed purchase, decision is made. We know that globally, 20% to 40% of crop production is still at risk to disease and weed pressure each year. To answer the seed selection opportunity, vast amounts of field-specific data are needed to make predictive recommendations to maximize product performance. This is where FieldView insight can inform customers' decision-making processes and then help them get the most out of their seed and crop protection purchase. For example, FieldView Seed Advisor models improved productivity by optimizing seed placement recommendations. Today, the models used for this are empowered by more than 6.9 million data points from more than 8,600 hybrids on more than 70,000 fields. That data translates into tangible value for the grower. In testing from 2017 to 2020, we could demonstrate a 6-bushel per acre yield benefit just from using the recommendations. So once the seed is in the ground, how can data science help protect that yield potential? If we look at an example in corn, we know that timely application of fungicide can make a big difference. Our data demonstrates that 74% of the time, farmers see a positive response from fungicide application. Helping farmers to improve their returns and productivity is at the heart of what we're doing by combining our products with data science. These are just 2 examples and we believe we are just scratching the surface of how big data could further inform grower decision-making to help them maximize sustainability, productivity and profitability on their operations. In summary, we have a long history of converting R&D into viable, value-added solutions for growers that enhance productivity and more efficiently use natural resources to produce a crop. You could see that from the leading positions we have established to date and the growth of our pipeline that builds a very strong foundation for us. We've covered a lot here today and it's only a fraction of what's to come. Truth is, there are more than 100 projects, thousands of hybrids and varieties and more than 100 formulations in development here at Bayer Crop Science. Truth is, there are more than 100 projects, thousands of hybrids and varieties and more than 100 formulations in development here at Bayer Crop Science. We've detailed many of these in the appendix of the handout for today's talk, where you'll find our pipeline organized by strategic business entity. So you can see how we'll drive growth in those segments. I hope you'll agree that we don't simply have the largest pipeline in the industry, it's the most productive and comprehensive. Each product and each project has a place and a purpose serving unmet needs and imagining better ways to farm. Thanks for joining us today, and we look forward to connecting with you in the year ahead.

Thanks so much, Bob. And Bob will be here also for our Q&A later on. So if you have any questions for him, now is your chance, enter them into the chat, and I'll ask them on your behalf later on in the Q&A session. All right. Now let's turn to Leaps. This impact investment unit of Bayer is represented as some of the global biotech innovation hotspots. Leap's team members are represented in Boston, Cambridge as well as in the San Francisco Bay Area. And then Europe, the team is spread between the Berlin campuses and the Basel campuses. The German capital, as you may well know, has become one of the most dynamic hotspots for tech and biotech start-ups in Europe. We now have Jurgen Eckhardt, who has a prerecorded presentation for you.

Welcome to Capital Markets Day 2021. My name is Jurgen Eckhardt, and I'm the Head of Leaps by Bayer, the impact investment unit of Bayer. I'm excited to share a little more about the vision of Leaps by Bayer and some of our recent achievements with you today. Also, I do not want to miss making you aware of the virtual Leaps exhibition that you will be able to access at any time from the main lobby of the virtual CMD experience. Leaps was created in 2015 to break through the impossible in life science investment in scale, risk and collaboration. We began with a mission that is fundamentally different from what other corporate venture funds are pursuing. We have invested more than $1 billion into a portfolio comprising over 35 companies. Some are new companies we co-founded, others are early stage investments in existing companies. All are developing technologies that could be both profitable as well as sustainable, helping to solve some of the biggest challenges facing humanity today. What really makes us unique is that we focus our investments on truly paradigm-shifting advances. Minority equity investment is our tool to drive this mission. Our significant and sustained investments in outstandingly ambitious innovation may well revolutionize our industry and ourselves. We should always be clear about our areas of expertise. We have the ambition to create Leaps based on our solid foundation of about 150 years in the life sciences. The Leaps team is tasked with finding those technologies that could change today's businesses, including our Bayer businesses, potentially shaping or transforming the industry and changing the world to the better. Because we strongly believe that as a leader, we have the responsibility to embrace change, to question existing paradigms, otherwise, we will be the ones being disrupted. And the time is now. You are probably aware of the potential of the bio revolution. Even now in a time where the world has pushed the pause button because of a global pandemic, we see how the fourth revolution is poised to dramatically impact health, agriculture and many other industries, and we are thrilled to be part of this transformation. Bayer and Leaps by Bayer are strong believers into the idea that man-made problems can only be tackled by man-made innovation. What does that really mean? At Leaps by Bayer, we have attempted to translate this idea into 10 ambitious goals. We call them the 10 Leaps for humanity. They represent the articulation of what we are trying to achieve with Leaps by Bayer. At the same time, the 10 Leaps encompass what we believe are some of the biggest goals that humanity is after today: curing genetic disease, preventing and curing cancer, finding ways to cure autoimmune disease are amongst them in the health space. So if you want to condense the thoughts down to a single statement for health, it means moving from treatment to cure or from treatment to prevention. In the past centuries the whole industry of pharmaceuticals, including Bayer, has tried to address diseases the with treatments to find ways to prolong a patient's life, but often without actually curing the underlying disease. Today, we can do more. At Leaps by Bayer, we strongly believe that with the technologies that are existing today, especially in the cell and gene therapy field, we have the ability and the chance to change that and really develop cures or preventative medicines that stopped the disease from developing even earlier. And along those lines, Leaps is placing investments in regenerative medicine, in cancer or to find ways to alleviate the global organ shortage. In agriculture, we follow a similarly ambitious goal. During the past century, this industry was faced with an extremely challenging task to end hunger and feed an ever-growing world population. In the 21st century, things have changed, and we are at the cusp of a biotech revolution. Technology may enable us to better nourish the still-growing world population, but at the same time, do this in a much more sustainable fashion. With our portfolio companies, we aim to create food and agricultural solutions that can provide better, more nutritious foods and find ways to produce those with dramatically less impact on the planet. The Leaps by Bayer Portfolio encompasses around 35 companies. To date, we have invested about USD 1 billion. The portfolio is fairly balanced between companies in agriculture, and those in the health space. I want to briefly steer your attention to a few of these companies. BlueRock is a great example because it illustrates the role Leaps is aspiring to have for Bayer. Leaps co-created BlueRock in 2016 around the promise of the induced pluripotent stem cell. 3 years later, Bayer Pharma fully acquired BlueRock, which was really the starting point for Bayer's own cell and gene therapy strategy. Similarly, the digital health company Care/of was fully acquired by our Consumer Health division in 2020 after a first investment by Leaps in 2019. These are 2 examples of how Leaps' investments help support evolving divisional innovation strategies. Leaps can be an important driver of the division's early breakthrough innovation portfolio and can position Bayer to better access next-generation technologies. Another aspect that makes Bayer, and especially Leaps, a unique player in the life sciences is that we uncover opportunities where technology applications could span across our core fields of business. A great example of this is, Arvinas, a company harnessing the protein degradation system of the cell to selectively remove target proteins. Since both Arvinas and Leaps strongly believe that the technology may be able to deliver benefits not only for patients, but also for plants, we teamed up to create Oerth Bio. Oerth is a joint venture that aims to develop a completely new category of crop protection tools in agriculture. Ukko is another example where technological innovation on the agricultural side may have a direct impact on patient health. Ukko is developing solutions that could free people from conditions such as gluten sensitivity or other food allergies. A question I get asked often is how Leaps is differentiated from what we do internally within Bayer with our innovation efforts in research and development. The answer is quite easy. Leaps invests into areas that are early, new and/or risky enough that a full M&A or license transaction would not make sense for the time being. We invest in areas where internal knowhow is limited and where we are better off to let teams operate at arm's length. However, this does not mean that closer collaboration or even M&As are not possible at a later stage. Basically, the Leaps investments are in the high risk, high-reward bucket of our internal innovation portfolio. We operate in alignment with the divisional strategies and activities with the clear ambition to provide positive impulses for our internal ways of innovating. In order to deliver on this task, we have a very short reporting line into the Board of management. And we operate under our own investment budget. Therefore, the role that Leaps has within Bayer is very complementary to activities in the divisions and in R&D. Just to give you a flavor of our work or the work of our portfolio companies, I'd like to briefly showcase 2 of them to you, eGenesis and Joyn Bio. eGenesis is a fascinating company that tries to address the global shortage of donor organs. It was actually a spin-off founded out of George Church's lab at Harvard, the godfather of modern genetics. In the U.S. alone, more than 180,000 people are in need of a donor organ. Globally, that number is closer to 2 million people and growing daily. To alleviate this problem, eGenesis is working on ways to grow nonhuman organs for human use. One of the key issues with the utilization of nonhuman organs is rejection by the body's immune system. In the case of pig organs, another additional issue arises such as the porcine endogenous retrovirus, or PERV, which can be transmitted to humans. eGenesis is using gene editing technology, CRISPR, in order to overcome these problems and is hopeful that they will be the first. Certainly, we believe they are the most promising who will enable sustainable organ supply for humans through nonhuman donor organs. eGenesis is trying to make this a reality in kidneys as a first step, but later, also for islet cells, liver, heart and even lung transplants. Being able to achieve this, to us, would be a major leap forward in medicine. Another company I would like to invite you to experience is Joyn Bio from our agriculture portfolio. I get really excited when I have the chance to talk about Joyn. Joyn Bio was created from scratch by Leaps in collaboration with Ginkgo Bioworks, one of the leading global players in synthetic biology. Joyn's state-of-the-art labs are in the Boston Harbor area in a beautiful old building right next to the ones of Ginkgo. The technology Joyn Bio is primarily exploring is called nitrogen fixation. The concept is at once very simple and extremely impressive. As you may know, nitrogen is one of the most important nutrients essential for every plant to grow. Most plant species take nitrogen from the soil through their roots. And since there is often not enough nitrogen in the soil, it needs to be added through nitrogen fertilizer, but nature gave us some great exceptions. Naturally, there are a few plants that are able to circumvent this paradigm. Peanut plants, for example, through soil microorganisms are able to absorb nitrogen from the air and not just from the soil. These plants can grow with much less nitrogen provided through the soil, which means less nitrogen fertilizer use. And why is that important? Because nitrogen fertilizer and the production of nitrogen fertilizer through the Haber-Bosch synthesis process, which was invented in the past century is one of the big sources for carbon emission that you can find on the planet. It is estimated to contribute somewhere between 3% to 5% of all global greenhouse gases. So in a nutshell, Joyn Bio's technology would enable microbes to expand that paradigm from the peanut plant into commercially more relevant crops like rice, wheat or corn. It may have the potential to dramatically reduce the amount of greenhouse gas that originates from large-scale agriculture. What a leap forward for humanity would that be. Those were the 2 examples I wanted to share with you today. There is much more. Our portfolio includes many, many exciting companies. And if you want to learn more, I would love to invite you to join our virtual Leaps by Bayer exhibition that you can find when you click on the link in the Capital Markets Day lobby. You will be able to learn about a number of other portfolio companies and hear from some of their CEOs about their vision, approach and why the technology represents a potential leap for humanity. In summary, Leaps is the impact investment unit of Bayer. We invest into technologies with the potential to change existing industry paradigms and even Bayer businesses. The Leaps by Bayer activities are guided by solving 10 Leaps for humanity. We aim to establish business models that balance profitability with sustainability. Leaps by Bayer has invested more than $1 billion of minority equity into over 35 portfolio companies. With its strategy to create sustainable breakthrough innovation, the Leaps by Bayer mission aligns with Bayer's focus on health for all, hunger for none and a clear ambition to develop the Bayer businesses towards an integration of business strategy and sustainability. Thank you very much for your kind attention.

I want to extend my thanks to Jurgen for those great insights. Leaps is such an exciting area for Bayer. Now last chance, if you have any questions, please enter them now into the chat for our 30-minute Q&A that will come up in a minute. Please remember that we will have about a 10-minute break before we come back. And then all of our experts will be joining us to answer your questions. We will be joined by Christian Rommel, Robert LaCaze, Wolfram Carius and Bob Reiter. We'll see you shortly. [Break]

Welcome back, everyone. Thanks so much for submitting your questions throughout the day. And I'd say, let's get started with our Q&A now. The first question that we have is -- goes to Christian. It's from Falko Friedrichs, Deutsche Bank. And the question is, when do you plan to move your P2X3 compound into Phase III trials? And can this drug become a blockbuster candidate if it successfully launches to the market?

Yes. Thanks for the question. We expect the first Phase IIb data for the program by the end of the year. And then I mentioned that we are committed in multiple areas. So the next round of data will come in the first half of next year. And we generate the data to make data-driven decisions. We see a lot of value in this program, and we are very committed. And I get from the question that you share the excitement and I -- the team and I, so we, too.

Fantastic. The next question I have is for Wolfram. It's from Michael Leuchten, UBS. And the question is, AskBio, if we would move to other vectors away from AAV, what would that mean for the business model and contract manufacturing setup?

Yes. Thanks for that question. I would say, first, AAV, obviously, is a safe platform for our delivery, which is proven to be on the market and will be within the market for quite a time. But the [ team ] augmentation has [ further ] components. The capsid, the AAV, the part of the promoters and also the genetic material. And of course, we are also working on this technology, very valuable technology platform on different alternatives for the delivery for the long term. So this was whatnot burden any value of this outstanding platform and experience we have, be it on the Doggybone part on the genetic materials, the excellence on the promoter side. So it would not harm the CDMO business because, of course, we would also be able to support that with new delivery methods if they are coming up and being really requested and being safe.

Great. The next question I have is for you, Bob. It's from Falko Friedrichs, Deutsche Bank. When is your herbicide with the new mode of action expected to launch to the market? And how many years of a head start do you have with your product versus your competition?

Yes. Great question. Thanks for the question. So obviously, we're really excited by the -- where we are with the product overall bringing for customers the flexibility of having 5 different modes of action is really for us, we believe, it's going to be a game-changer. We're targeting a launch around [ '26, '27 ], pending various regulatory approvals. And we think that we clearly have a leading position because no one else really is describing anything like that, that they're going to be able to bring to farmers. So we're laser-focused. I think that's one of the advantages of having such an advanced pipeline like ours. It really gives us the opportunity to drive not only the trade approval for the trade itself, but also to be able to then focus our breeding programs. Because at the end of the day, farmers don't just buy traits. They buy performance in weed control in a single package together, and that's really key for us to be able to deliver that performance advantage with our genetics, together with the flexibility that the trait package will provide for weed control. So super exciting, and we're well on our way, and we're going to get our farmers excited as well.

Next question I have is for you, Robert. It's from Michael Leuchten, UBS. A Vitrakvi competitor has entered the market at a much lower price. What impact has that had on the market?

So thanks for the question. The -- when you think about TRK fusion, the biggest driver here is patient [indiscernible] has a rare tumor. And price has not really been a key factor for the treatment of these patients. We've even found that when you actually take the compound, you look at the clinical data, the really important part is not just response rates, but look at how long these patients respond, they respond for a long period of time. Vitrakvi was actually the only TRK inhibitor that's a specific TRK inhibitor in the market. Some of the other compounds are multi target kinase inhibitors. So they hit different pathways and not just TRK. And the other thing that makes Vitrakvi different is it's the only one that also has a pediatric indication and a pediatric formulation. So when prices come up, and we've been able to have direct discussions with the medical departments at their different payers, they understand the true value that Vitrakvi brings to the patients that we've been able to maintain the value proposition of the compound.

I have a question here for Christian from Jo Walton, Credit Suisse. How do you price a drug which has possible indications that range from chronic cough to diabetic neuropathy? Should we think that other possible indications will be prioritized to move to Phase III?

I appreciate the question, but I think it's too early to get into details here. We really want to first further build momentum on the data and bring the evidence and the mechanisms of the molecule. And then although, as working in R&D, I will work with my colleagues from commercial, but I know we know how to do this, and we hope we can get there and give you the answer anytime soon, but not yet.

I have one more question for you from Richard Vosser, JPMorgan. What differentiation do you see from your exon 20 inhibitor compared to Johnson & Johnson's development product?

I'll take that question differently. I think what an opportunity first, right? We all know the value of oncogenic drivers and then providing treatment options for patients that have these kind of molecular drivers that are also resistant to current standard of care. So I think we have to work on that. We see an opportunity here to provide the molecule therapeutic solution to what really thrives the tumor. And if you have a receptor tyrosine kinase inhibitor, you hit the target where it matters most, in the activity of this oncogene. So that is what we signed up for. Something I think our chemists are very good at. And we think that we will not sit still until we have a quality like Vitrakvi that Robert just mentioned. And we're very confident to provide the data that this is doable. And I really go here with the opportunity and the unmet need. And hitting again, hitting the tumor where it matters most and a resistant oncogenic driver is exactly what it's supposed to do and I think we are doing that.

Great. Thank you. I have a question now for you again, Robert, from Jo Walton, Credit Suisse. For Nubeqa, you have highlighted the biggest patient opportunity in adjuvant with a 2028 study completion. How much of your $1 billion peak is dependent on success in this indication?

So let me just maybe frame out the prostate market itself so we can get a understand of how all the drugs may flow through the marketplace from a patient standpoint. So if you think about the nonmetastatic castrate-resistant prostate cancer area, that's where Nubeqa is currently approved. These men are -- they have cancer that's actually beginning to progress. And typically, when you look at the clinical trials, the men stay on these -- on the therapies for 3, maybe 4 years, so a fairly long period of time. When you go into the adjuvant side -- and these are, most of the time, newly diagnosed patients who have not necessarily seen the drug therapies yet, but they're getting their first drug treatment. Oftentimes, they're using a drug regimen of ADT, maybe some radiation, surgery. And so what we're looking at in this population -- and this is normally a very, very fit population, a healthy man. And so with Nubeqa, what we're looking at is adding it to their current treatment. Normally, in this setting, the treatments are only for a short period of time, maybe 8 months to 12 months. So they're not only until progression. So it's a much shorter period of time. So overall, even though there's a bigger number in the adjuvant setting, as we think about the opportunity in the adjuvant setting, it's not as large as what it would be in the later lines, just [indiscernible] shorter duration of therapy. So a lot of the -- so as we think about the overall contribution to the upside on the cells, it's really more in the in the nonmetastatic and the metastatic setting. Now with that said, the reason why this is an important therapy is if you think about these men, and if you can actually prolong progression-free survival or even metastatic-free survival or maybe even overall survival, you need to do this in such a way where you're not adding burdens and side effects. And that's what makes Nubeqa so especially important treatment option or therapy, assuming that the data is positive, in order to give a much earlier line of treatment with a profile that can be -- that's needed for this patient population. And Ariane, one last thing that I wanted to just mention. You were asking about Vitrakvi earlier, I was speaking more for the U.S. market in terms of the price. I just wanted to transition back to that question because I forgot to answer the question from a European standpoint. In Europe, as you know, the price is driven mostly by HTAs because there's a whole different dynamic that occurs in Europe as we think about the pricing. So I just want to make sure that I clarified the earlier answer was more specific to the U.S. and then we go through the appropriate HTA type of negotiations from a European standpoint.

Super. Thanks for that clarification. All right. Moving on back to you, Bob. Christian Faitz from Kepler Cheuvreux has a question. Will there ever be a replacement for glyphosate in terms of trait herbicide combination that does away with the current weed-resistance issues?

We also get asked the question about glyphosate and what's -- when is the next glyphosate coming? And the reality is I would say glyphosate was a once in a lifetime discovery. It's a reflection of today why it's still such a popular herbicide with farmers. It continues to be really, I would say, the pillar of their weed control systems. What I would say instead is, is that what we're probably going to see is how do we better leverage all of the data and insights we have around weed control and help growers think about weed control differently. Because today, what we do is we provide growers with a drug of different chemistry options, we try to describe to them how to best use those. But we don't really help them, I would say, think about holistically, we control management over a multiyear period and in a way that really both fosters weed control for them on an annual basis, which is what they're trying to get done. But also more importantly, weed resistance. I don't care what the chemistry is and glyphosate is a perfect example. Mother nature will survive and it will figure out a way to overcome solutions that we tried to bring to the market that farmers try to use. So I think the opportunity really here is, how do we provide growers with very integrated systems and also offer them solutions that are more outcome-based? And I think that's one of the exciting things as I think about our tools, where we're going to provide multiple modes of action for flexibility. And we provide data insights and to think about what are the right solutions you want to use before you ever plant? And what are you going to use after you plant? How can we do that more precisely and more environmentally friendly? And how do we do it in a way that manages weeds, thinking about the long term? All that is really complex stuff. And I think it's really, I would say, where the frontiers are going to be in terms of weed control. It's really going to be about bringing holistic solutions as opposed to trying to invent one new solution that we think is going to be the savior for us in the future. It's really about a systems approach in my view.

Next question goes to Christian from Jo Walton, Credit Suisse. You acquired KaNDy with a [ P3-ready ] asset with EUR 100 billion peak sales for only $425 million. In such a competitive market for pharma M&A, why do you think others were not interested in this blockbuster?

I think here the -- see the opportunity when you are a leader in an area. So Bayer Pharmaceutical, Bayer is a leader in women's health. And this comes not only a track record of [ modern ] important medicines and the portfolio comes also with a standing that you have your network of investigators, you have physicians, there's so much that makes us magnetically attractive to assets and opportunities for partners. I think I can share that has been a competitive process. It didn't come for free. But I thought the most compelling for the science we represent, our values and our leadership, and we are now proceeding with a full commitment. And I think we -- that, I think, was the reason why the team from KaNDy thought to work with us and give us the [ baby ] in our family was the best idea. And I agree with them.

Okay. Next question is for you, Wolfram. James Quigley from Morgan Stanley asks, how large is the Viralgen CDMO business within AskBio? Who would you say the key competitors are? And could you give us an idea of the market share of Viralgen in its key markets?

Sure. Yes. I mean I think it's known to all of us that the capability and also the capacities to develop and manufacture the products in the cell and gene therapy area is absolutely key. And the CDMO market is really growing in high double-digit percentages. So the differentiator in this market is clearly a track record on part of quality and safety and on-time to market. And I think with Viralgen, we have a world-class position there. Integrated very deep supply chain, being able to really assist and help people to bring product to the market. We strive for around [ EUR 80 million to up to EUR 100 million ] sales, but that is the very beginning of the journey in a super dynamic market, where we already started to quadruple, for example, our capacities in the CDMO business. Main competitors are, I think, widely known. It is Thermo Fisher being very active through various acquisitions in the last years. Its Lonza, with a second attempt to bring that on to the market. These are the main 2, I would mention.

Back to you, Christian. A question from Michael Leuchten, UBS. There's always been good science at BionPharma, but the organization has managed to take immense commercial battles in markets that require building them from scratch, what can be improved from this perspective? Does it need to be improved?

Yes. Thanks for mentioning the quality of our science or the innovation we do. Again, I agree. I noticed the company since a few weeks, and that's what I found, good quality science and innovation. I think with story and track record of Xarelto or EYLEA, we have shown improvement that we can take on those opportunities, right? We see the opportunity and the challenge when going into these large indication markets. And I can tell you, if you see another opportunity that is built on great science and addresses an unmet need to do this again. We can do this on our own, or we can do it in a partnership, but we will not miss an opportunity to make an impact for patients and then on Bayer.

A question for you, Bob, from Christian Faitz, Kepler Cheuvreux. Nitrogen fixation, what is the market potential in your view?

Yes. So obviously, fertility, particularly in a crop like corn, is super important. Wheat would be another example of that. So we're talking the potential for potentially hundreds of millions of acres, if you look at just those 2 crops alone worldwide. The question, of course, is going to be is how much do they help, right? So -- and microbes that have nitrogen fixation and are going to help the crop in terms of capturing nitrogen from the air and then providing it directly to the plant. They're going to -- it will be dependent on how much of the nitrogen offset that they're creating versus providing synthetic fertilizers and the price of that fertility, there could be some synergistic effect candidly between fertility that's applied and the nitrogen fixation and the nitrogen that gets supplied through the nitrogen fixation process. And then I think the third element, which I think is maybe even more important in this whole opportunity space is nitrogen is a very big contributor to the overall climate change impact space as we think about agricultural production. And so how do we better optimize nitrogen use? And I think these kinds of tools, I think, are going to be really critical as we think about some of our sustainability goals that bear and how we want to help our farmer customers be more environmentally sustainable. If we can leverage these tools together with how fertility is applied, which I think is how ultimately -- how I ultimately see these things working together. I think huge farmer interest and hundreds of millions of acres that the space of the application is available. So big idea, lots of excitement, lots of big opportunity, but still obviously a long way to go technically.

Christian, back to you. Question from Jo Walton, Credit Suisse. You're excited about your ATR drug, how is it differentiated versus others?

So why I'll be excited? DNA repair is amongst the most important hallmarks of tumor biology. The [ counter ] is able to deal with 2 major surveillance mechanism, immune surveillance and DNA integrity surveillance. And we see an opportunity to, again, hurt the tumor where it matters most. We want to block the -- this escape mechanism and block DNA repair. So in addition to this is that understanding the molecular genetic networking relationship, the synthetics so-called relationships gives us 2 opportunities. One is to identify the patient population to tumor type. But most important here, the patient population that is most likely to be sensitive and respond best to such a therapy. And that is part of how we design and pursue our Phase I development. And that's the kind of science we need to do in the clinic. So if we can build confidence, can get data and make decisions, whether we go all in and go forward or maybe not. And here, we believe that this is the opportunity. Second is the DNA repair mechanism. ATR by itself offers opportunities for combination therapies. And we are pursuing that. How will it be different and better? I think you have a very fine molecule. I think I mentioned in my presentation, that I'm very impressed about the quality and the track record. There's almost a historic knowledge in Bayer on small molecule drug discovery. And I now see a high quality. So we -- in this program, we can focus really on the target. On target mechanism, on target safety so that will enable us. And then we have to, of course, bring the evidence in the data, but we are now committed to do that.

Bob, back to you. A question from Vincent Andrews, Morgan Stanley. With one of your competitors planning to launch an insect trait in Brazil, what's different about the Brazil soy market versus the U.S. soy market that we need to not worry about increased competition like we've seen in the U.S. with Xtend and Enlist?

Yes. Thanks for the question, Vincent so they are very different kinds of markets. And so here are some of the main differences. So first of all, the soybean market, as we think about traits in Brazil, it's really about insect control. That is the thing that drives some of the decision-making and what the grower really values in the Intacta platform and our franchise down there today, which is very well established. So that's the first piece. Insect control is number one, weed control would be #2. The second piece is the weed control dynamics in the 2 geographies are quite different. So in the North American market, the attractiveness of additional systems that complement the Roundup Ready system were really driven by some broadleaf weeds, which do not have the same presence in South America. So some of the -- as we launch our Xtend platform or we see competitor platforms being launched, the core still for the grower down there is going to be glyphosate and using Roundup over the top. They will have the opportunity to use the Xtend platform to do some minor cleanup. But the key there, really, they worry about grasses more than they worry about broadleaf weeds. So they have a different weed spectrum. And then the third piece for me is that given that we have such a well-established Intacta platform, and we have such a good seed footprint together with our partners there, we're very well-established in driving the genetic performance that goes behind as we launch Intacta to Xtend and given the support we have of the key genetic partners and our own footprint there in South America, and the fact that our insect protection has 3 modes of action, which is really compelling for the grower in terms not only of excellent insect control, but broader insect control spectrums than they've experienced with the first generation Intacta, we feel that we're in an excellent competitive position. So very different dynamics. We feel really strong about our position. We're obviously launching later this year, given that we have all the regulatory approvals as well. And we've got terrific genetics. So we're really excited by that. And I think our customers are going to be really pleased.

Okay. I come to the final question of this Q&A, and it's for you, Christian. It's from Peter Verdult, Citi. What has happened to the Dimension Therapeutics hemophilia gene therapy project?

I think only good things so far. Ultragenyx acquired the asset from Dimension. So the program is active. It's in Phase II, and we'll provide update. It's an active program, and we are working with Ultragenyx on it.

Great. Thank you very much. Well, on that note, our 30 minutes are already over. I want to thank you so much for your time and your insights. We didn't get to all the questions. So absolutely, the Investor Relations colleagues will follow-up on any questions that were not answered during this event. Big thanks to you again.

Thanks to you too, Ariane.

Thank you. This concludes our second and final day of Capital Markets Day 2021. And with this, I'd like to hand over to Oliver for some closing remarks.

Thank you so much, Ariane. I hope that you all enjoyed our Capital Markets Day. As you have seen during the past 2 afternoons, Bayer is accelerating its transformation to create sustainable value towards 2024 and beyond. I hope that you share our excitement about the future prospects of Bayer, and I hope to see you all soon in person again. I would like to thank you all for your time and attention during those days. And Ariane, it was an absolute pleasure to have you here with us. Thank you so much. And I'd like to thank you for your very professional moderation actually today.

Well, Oliver, the pleasure was truly all mine. As we mentioned before, you can now access all of the presentations, materials, videos in our resource center. For those of you who registered for a coffee break, we will continue that after a short break at 5:30 p.m. CET. And so just use your individually shared teams invite for that. All of the others are, of course, invited to explore a platform exchange in the chat lounge or also take a look at the Leaps exhibition, and our Leaps experts are going to be available for you again in the chat lounge from 5 until 7 p.m. CET to answer any Leaps-related questions that you may have.

We now say goodbye from the communication center here in Leverkusen, and we wish you guys all the best. Have a good rest of the day and stay healthy and safe. Bye-bye.

Bye.