STAT3 x Nrf2

Bayer is applying its new operating model for key drugs elinzanetant and Nubeqa. Bayer’s massive reorganization championed by CEO Bill Anderson is bringing major changes to the German company’s pharma commercial team, shaking up its structure, personnel and operations. “We are transforming from a company that has been largely focused on hierarchy within functions to an organization—and supporting design—that really focuses on customers and products,” Christine Roth, head of global commercialization at Bayer’s pharmaceutical division, said in a recent interview with Fierce Pharma. Roth’s promotion to her current position was part of the restructuring as Bayer shrank its pharma executive team. The former oncology business chief officially started to lead a newly formed commercialization organization on June 1. The purpose of the groupwide overhaul was to reduce Bayer’s levels of bureaucracy, as job reductions were expected to mainly affect managerial roles. The new operating model, dubbed “dynamic shared ownership,” or DSO, promises fewer organizational layers and more agility for employees. While layoffs across Bayer are not expected to finish until 2025, Roth said headcount reductions in the pharma commercialization unit will largely be done at the beginning of the fourth quarter.   A new operating model As a result of the streamlining, “the span of coaching for every leader in the organization is going to double and, in some cases, triple,” Roth told Fierce Pharma on the sidelines of the American Society of Clinical Oncology annual meeting in Chicago in late May. “One of the tenets of DSO is, managers need to be less involved in the day-to-day,” Roth said. “Our role is as visionaries, architects, catalysts and coaches.” Within Bayer’s pharma unit, staff responsibilities across late-stage development, registration, commercialization and lifecycle management are being reshaped, with regulatory and development functions shifting over to the R&D organizations. For commercialization, Bayer previously had product sales teams and parallel functional teams, which may have operated on separate strategies. Now, those functions, such as marketing, market access, medical affairs and patient advocacy sit unified in the global capabilities group—instead of being dispersed across each product. Under that model, Roth explained, the product teams will set goals, and then everyone else, including Roth herself, will provide resources in service of those goals. The new DSO model still needs some honing, but Bayer expects to install people in their new jobs and functions by the end of the year across the company, Roth said.  “The beauty of this system is, we’re not perfecting it before we start,” Roth said. “We’re getting to a good place where we can start to experiment and go. And we will learn and adjust as we go.” To help test out DSO, Bayer has designated several “front-runner” teams. “The front runners have been really critical in helping us do that, because their job was to try out the new system—we did our best to completely leave them alone—to let us know what’s working to support them and what’s not working, and then feed real-time learnings back into the organization,” Roth said. The team for Bayer’s prostate cancer drug Nubeqa is one of the front-runners groups. Bayer has pegged the androgen receptor inhibitor to reach peak sales of more than €3 billion a year. Bayer is trying to expand Nubeqa’s reach in part through the phase 3 ARANOTE trial in metastatic hormone-sensitive prostate cancer. The study reached primary completion on June 7, according to clinicaltrials.gov. A Bayer spokesperson said the company plans to announce the topline results soon. While preparing for potential regulatory filings for ARANOTE, the team identified many unnecessary processes from the old practice, including around 80 tables that would have previously been produced. Eliminating those processes will save time and costs, Roth said. DSO is also coming into play with Bayer’s possible launch of the hot flash drug elinzanetant, which has three positive phase 3 trials in the bag and an FDA filing on the horizon. The new model has allowed the elinzanetant staffers to tap into digital resources that traditionally have not been dedicated to a specific product team, Roth said. Novel channel marketing resources were brought in “because they see this launch as not so much the traditional boots-on-the-ground, reach-and-frequency, face-to-face with physician, but much more patient engagement and much more policy engagements,” Roth said. Direct-to-consumer patient marketing will be critical for elinzanetant launch, Roth added. Bayer wants to empower women to have an open dialogue with doctors about their symptoms and potential treatment options, and to make sure medical policies are in place so that patients can have access to the meds. Bayer is evaluating DSO system in 90-day cycles. According to Roth, employees are getting the hang of the new model and need no more convincing. “We are going to have to get our hands dirty and let teams really struggle through some of these things before we see what kind of adjustments we need to make,” Roth said. “What I am very focused on achieving between now and the end of the year is, as people complete multiple 90-day cycles, I will be listening and checking to make sure that it feels different for employees. They feel empowered. They feel like there are fewer barriers to getting the job done. They feel like they’re closer to the customer.”   Bayer’s oncology ambition: ‘A moving target’ Roth had experience working in women’s health and cardiometabolic diseases. But before she came to lead Bayer’s entire pharma commercial operations, she had spent nearly two decades in oncology, including at GSK, Novartis and Bristol Myers Squibb. Last year, Bayer laid out an ambition to reach $10 billion in revenue from cancer drugs by 2030 and to become a top 10 oncology player. It’s a bold target considering none of the pharma division’s top 3 products last year were in oncology, while Nubeqa is expected to hit above $1 billion sales this year. So at last year’s ASCO annual meeting, Roth told Fierce Pharma that Bayer would need a “midsize acquisition” to reach its revenue goal. This time around, Roth argued that there’s no magic formula on how to achieve an ambitious target in pharma, and that a midsize deal may not be absolutely necessary. “I would not so much focus on the $10 billion anymore,” Roth said during this year’s ASCO conference. “The goal is to become a top oncology player, and it’s a moving target anyway.” “All we need, to be quite honest with you, is [for] one of the assets from Vividion—one of the assets in our pipeline—to be our next $2-to-$3-billion drug,” she said hypothetically. “And all of a sudden, the picture changes.” Bayer acquired Vividion Therapeutics in 2021 and made the discovery engine an independently operating subsidiary. In oncology, the unit is working on candidates to inhibit NRF2 and STAT3, and it has an anti-WRN program in collaboration with Roche. But all of those programs are in early-stage testing and currently don’t have data in their clinical profiles. Roth also pointed to Bayer’s HER2 program, a reversible tyrosine kinase inhibitor coded BAY 2927088, which recently received an FDA “Breakthrough Therapy” designation in previously treated HER2-mutated non-small cell lung cancer. It also has a new PSMA-targeted radioligand therapy coded BAY 3563254. But those are also in phase 1 development. Compared with other therapeutic areas, Bayer’s oncology pipeline is composed of newer assets that are relatively unproven. In women’s health, the company is looking to introduce elinzanetant soon. And it just bought European rights to BridgeBio’s near-to-market heart disease drug acoramidis. But in oncology, it has no phase 2 or phase 3 therapeutic programs in sight for novel molecules, while Nubeqa was first introduced about five years ago.   The Bayer pharma team has had discussions with CEO Anderson—a pharma veteran—about the need to balance between early-stage and later-stage assets in the oncology pipeline, Roth said. For one thing, the DSO model is expected to advance early-stage programs faster. “The core of the strategy is really to continue investing and filling the funnel,” Roth said. As for M&A deals, Roth argued that the ongoing restructuring wouldn’t impair Bayer’s ability to pursue external transactions in oncology, pointing to the BridgeBio deal. But the drugmaker simply hasn’t identified the right target. “[If] we find the right one, I’m fairly optimistic that we’ll be successful if that’s what we want to bring in,” Roth said. “We’ve looked at a lot of things that have transacted recently and just decided for one reason or another that they weren’t the right deal for us.”

At its annual Pharma Media Day 2023, Bayer presented the latest progress in the ongoing transformation of its pharmaceutical business focusing on accelerating innovative healthcare solutions for the benefits of patients and delivering long-term, sustainable business growth. "The transformation of our Pharma business is progressing well. With bold investments in industry-leading technology platform companies, we have bolstered our R&D capabilities and strengthened our early development pipeline," said Stefan Oelrich, Member of the Board of Management, Bayer AG and President of Bayer's Pharmaceuticals Division. "Going forward, we will focus on realizing the full potential of our projected blockbuster candidates Nubeqa, Kerendia, asundexian and elinzanetant. We will specifically allocate resources to grow our oncology and cardiology businesses in the U.S. The implementation of our strategy aims to deliver new medicines to patients faster and drive sustainable growth across our key areas of focus." During this year's Pharma Media Day 2023, Bayer showcased how its investments in strategic technology platforms accelerate its medical and digital innovations and will advance the company's leadership ambitions in cardiology, oncology, and radiology. In addition, Bayer provided insights into its innovation strategy, comprising enhanced research and development (R&D) capabilities in key areas. "Patient needs, precision therapies to address disease complexity as well as advances in science and technology are evolving rapidly. Therefore, we are evolving our R&D strategy and operating model to focus on differentiated, high-value breakthrough medicines," said Christian Rommel, Member of the Executive Committee of Bayer's Pharmaceuticals Division and Head of Research and Development. "Moving forward, we will focus our early research activities on core strategic areas: oncology, cardiovascular, neurology & rare diseases and immunology, where we believe we can make the biggest possible difference for the patients we serve." Delivering significant growth through a leadership position in oncology The company has doubled its portfolio of oncology treatments over the past five years. With Nubeqa (darolutamide) as a key growth driver it is gearing up to become a leader in prostate cancer, the second most commonly diagnosed cancer in men. Nubeqa has the potential to become the standard of care for prostate cancer patients from the early- to the late-stage of this disease. Going forward, growth of Nubeqa will be driven by recent approvals for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC) in the U.S., EU, Japan, and China. In parallel, the robust Phase III clinical development program with darolutamide aims to broaden its use from the metastatic into the earlier disease stages, e.g. in patients with hormone-sensitive prostate cancer with high-risk of biochemical recurrence and as an adjuvant treatment for patients with localized prostate cancer with very high risk of recurrence. The company has projected a peak sales potential for Nubeqa of more than three billion euros. "With Nubeqa's potential to set a new standard of care in prostate cancer, its compelling clinical program across the spectrum of prostate cancer and our growing early pipeline, we are well placed to deliver on our commitment to bring innovative medicines to cancer patients," said Christine Roth, Member of the Executive Committee of Bayer's Pharmaceuticals Division and Head of the Oncology Strategic Business Unit. "Bayer has clear ambitions to become a top oncology company. We are investing in innovative treatments and modalities that have the potential to be transformative for a broad range of cancer patients, who currently have little or no treatment options." Bayer is advancing its oncology R&D efforts in three scientific areas that have the potential to address unmet needs in cancer patients. This includes targeted radiopharmaceuticals (specifically targeted alpha therapies), next-generation immuno-oncology and precision molecular oncology approaches. In these areas, the company is advancing truly first-in-class, highly innovative projects in its portfolio. Nearly one third of new molecular entities within Bayer's development pipeline is dedicated to fighting cancer, spanning all phases of clinical development. With recent major investments, Bayer has fortified its oncology innovation engine substantially. The new $140 million Bayer Research and Innovation Center (BRIC) facility, located in the center of thriving Boston-Cambridge, Massachusetts, is home to Bayer's precision molecular oncology research group, fostering collaborations in this outstanding U.S. innovation hub, including with the Broad Institute of MIT and Harvard. Vividion Therapeutics, which Bayer acquired for $1.5 billion, comprises a leading chemoproteomics platform capable of identifying previously unknown binding pockets in undruggable targets to generate first-in-class novel drug candidates in indications of high unmet medical need. This technology and the unique approach of an innovative arms-length operating model have the potential to accelerate the timelines to get assets into the clinic. For the first two programs, which are addressing high profile cancer targets NRF2 and STAT3, Vividion is expected to file the Investigational New Drug Application (IND) in the U.S. in 2023. Developing the next generation of cardiovascular therapies The short- to medium-term growth in the area of cardiovascular (CV) diseases will be driven mainly by Kerendia (finerenone), a non-steroidal, selective mineralocorticoid receptor antagonist, representing a valuable treatment option for patients with cardio-renal disease. Kerendia is already approved in major markets in chronic kidney disease (CKD) associated with type 2 diabetes. Bayer has exclusive worldwide marketing rights for this product including the U.S. The ongoing development program to expand Kerendia into additional indications comprises three Phase III studies: FINEARTS-HF, which investigates the compound in patients with symptomatic heart failure with preserved ejection fraction; FIND-CKD, with the goal to make the medicine available also to patients with non-diabetic CKD etiologies including hypertension and chronic glomerulonephritis (inflammation of the kidneys); and FIONA, which investigates finerenone in pediatric patients with CKD and severely increased proteinuria. Kerendia is estimated to generate peak sales of more than three billion euros. Bayer's investigational treatment of cardiovascular diseases asundexian is currently in Phase III clinical development. Asundexian is an oral Factor XIa (FXIa) small molecule inhibitor being investigated in patients with atrial fibrillation (AF) as well as in patients with an acute non-cardioembolic ischemic stroke or high-risk transient ischemic attack (TIA), a temporary period of symptoms similar to those of a stroke. The respective Phase III clinical trial program, OCEANIC, which has recently started enrolling patients, is one of the largest conducted in the company's history. Asundexian, which belongs to a new class of drugs, has a projected peak sales potential of more than five billion euros. "Cardiovascular diseases can have a significant impact on patients' lives. We are advancing highly innovative projects in our portfolio to address patients' high unmet medical needs and shape the future in cardiology," said Christian Rommel, Member of the Executive Committee of Bayer's Pharmaceuticals Division and Head of Research and Development. "The number of innovative approaches and novel modalities in our portfolio will triple in future. With those we will be able to target pathologies and disease mechanisms that were not druggable before." Building on its strong late-stage projects, the company has set a clear directive towards precision cardiology, exploring innovative approaches across a diverse range of modalities, with the aim of pushing the boundaries of innovation for patients with cardiovascular diseases with high unmet needs and potentially reversing life-altering conditions. Complementing in-house expertise with external collaborations remains a vital part of Bayer's strategy to expand its R&D expertise and develop robust cardiovascular therapies, with the goal of addressing high unmet medical needs across broad indications, including specialty cardiology and rare indications. Through Asklepios BioPharmaceutical Inc. (AskBio), Bayer is developing a gene therapy as a potential new approach for treating congestive heart failure. With the acquisition of AskBio, Bayer gained access to an industry-leading gene therapy platform with demonstrated applicability and world-class manufacturing facilities. Beyond congestive heart failure, AskBio is also currently advancing four clinical-stage and a number of preclinical candidates addressing medical need indications across a diverse set of diseases such as Parkinson's disease, Pompe disease and Huntington's disease. Bayer's advancements in cardiovascular disease are enabled by digitalized, decentralized and more diverse clinical trials, as well as partnerships on industry-leading sources of data, such as the Accelerating Medicines Partnership in Heart Failure and the Broad Institute's Precision Cardiology Laboratory. These initiatives are helping to accelerate the discovery of new molecules and bring new treatments to patients that need them. Leveraging digital innovation to support diagnosis and drug discovery Bayer is implementing its innovation strategy in radiology, with a key focus on digital medical imaging and artificial intelligence (AI). The medical imaging AI market is the fastest growing segment within the global radiology industry. The estimated compounded annual growth rate is more than 26 percent reaching $1.36 billion in sales by 2026.1 A cornerstone of Bayer's ambition is its recently launched platform Calantic Digital Solutions, which delivers access to digital applications, including those powered by AI. It provides an ecosystem of third-party and Bayer products to deliver disease-oriented solutions for radiologists and their teams. The platform is designed to support healthcare professionals at various stages of their work, from diagnosis through treatment of their patients. To bolster its position in the medical imaging AI market, Bayer recently acquired the global strategic imaging AI platform and solutions provider Blackford Analysis Ltd, which will operate under Bayer's well established "arm's length" operating model. Utilizing Blackford's and Bayer's combined expertise in healthcare technology, this acquisition fosters Bayer's engagement to drive digital innovation in healthcare, with the aim to deliver true value to radiologists and their teams for the benefit of their patients. "Building on a deep medical expertise across a multitude of diagnostic and therapeutic areas, Bayer is a leader in key radiology segments with a comprehensive portfolio that generated close to 2 billion euros sales in 2022," said Gerd Krueger, President Radiology, Bayer. "Expanding our offerings into the field of AI further advances our strong position in this market. It follows our mission to deliver disease-oriented solutions for patients and their physicians. The transformative expansion of our radiology business is a key element of Bayer's accelerated digital transformation, which strategically leverages data science and advanced analytics across the value chain." Bayer is investing to leverage the power of data and rapidly evolving technologies such as artificial intelligence throughout the entire pharma value chain, from discovery to production. The company is partnering with technology leaders such as Google Cloud and biotech leaders such as Recursion Pharmaceuticals, Inc. to access new areas of innovation. In addition, Bayer has built up extensive in-house expertise to transform its development, manufacturing and medical operations to better serve the needs of patients, healthcare professionals and healthcare systems with relevant innovative solutions. Bayer works on leveraging all the possibilities of the technologies while fully integrating all regulatory and bioethical requirements. About Bayer Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. Its products and services are designed to help people and the planet thrive by supporting efforts to master the major challenges presented by a growing and aging global population. Bayer is committed to driving sustainable development and generating a positive impact with its businesses. At the same time, the Group aims to increase its earning power and create value through innovation and growth. The Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2022, the Group employed around 101,000 people and had sales of 50.7 billion euros. R&D expenses before special items amounted to 6.2 billion euros.

Bayer said Friday that it plans to concentrate its drug research efforts on oncology, cardiovascular, neurology, rare diseases and immunology, while pivoting away from women's health, long a key area for the company. Stefan Oelrich, head of Bayer's pharmaceuticals unit, said during an annual media day event Friday that "when it comes to research and the subsequent clinical phases, we will no longer have an explicit focus on women's health."Oelrich noted that some projects in immunology could still yield products in women's health, but Bayer's dedicated work in this particular area overall had fallen short of expectations. The shift comes as ex-Roche executive Bill Anderson is set to take over the top job from Bayer CEO Werner Baumann in June (for more, see Spotlight On: Bayer breaks with tradition to appoint pharma-focused CEO).The company currently markets the Yasmin/YAZ oral contraceptives, and indicated that it will still continue working on elinzanetant, an oral non-hormonal drug currently in Phase III development to treat vasomotor symptoms during menopause, as one of its four most promising pharmaceutical products. Last year, it also expanded the OASIS programme for elinzanetant to include breast cancer patients with vasomotor symptoms caused by endocrine therapy.Among other products it is hoping will drive future growth are the prostate cancer treatment Nubeqa (darolutamide) and chronic kidney disease drug (CKD) Kerendia (finerenone), both already on the market and projected to generate combined peak sales of €6 billion ($6.5 billion). It also estimates that its once-daily oral factor XIa inhibitor candidate asundexian, which recently entered Phase III for stroke prevention, will bring in more than €5 billion ($5.4 billion) at its peak. Elinzanetant, meanwhile, is expected to earn up to over €1 billion ($1.1 billion) in revenues."With bold investments in industry-leading technology platform companies, we have bolstered our R&D capabilities and strengthened our early development pipeline," said Oelrich, adding "we will specifically allocate resources to grow our oncology and cardiology businesses in the US." He noted that recent deals to become a major player in cell and gene therapy has resulted in a bigger role for neurology, rare diseases and immunology.In oncology, Bayer said it is focused on radiopharmaceuticals, particularly targeted alpha therapies, as well as next-generation immuno-oncology and precision molecular oncology approaches. It noted that nearly one third of new molecular entities in its pipeline is dedicated to fighting cancer. The company also highlighted its 2021 purchase of Vividion Therapeutics for $1.5 billion, saying it expects to advance into the clinic the first two programmes – targeting NRF2 and STAT3 – stemming from that acquisition after it seeks FDA authorisation to do so this year.Regarding cardiovascular therapies, Bayer's head of R&D Christian Rommel said "the number of innovative approaches and novel modalities in our portfolio will triple in future." The company's ongoing Phase III development programme for Kerendia is looking to expand into other indications, including paediatric patients with CKD, patients with heart failure and those with non-diabetic CKD etiologies.Oelrich also shared thoughts on expected EU pharmaceutical industry reforms. A planned revision of drug legislation in the bloc was recently delayed, and the executive indicated he hopes that leaves open the door for EU officials to reconsider a decision to cut intellectual drug property protection. Earlier this year, Oelrich said decisions by EU and UK policy makers were turning the continent into an "innovation unfriendly" place to do business, and prompting Bayer to shift the focus of its drug unit to places like the US and China instead.