January 14, 2020
• Emerging leadership in field of cell and gene therapies
• Accelerating breakthrough innovation for patients
• Innovation in field of digital health solutions to become key pillar of Bayer’s pharmaceutical business empowering patients with Integrated Care offerings • Promising development portfolio with more than 50 projects in clinical development phases
At its virtual Pharma Media Day, Bayer presented exciting progress in transforming its pharmaceutical business with breakthrough innovation in healthcare that will significantly help patients suffering from conditions that are currently still difficult to treat. The company has recently heavily invested in external innovation with an unprecedented number of more than 25 collaboration agreements and acquisitions.
“The biomedical and technological revolution that is transforming healthcare at an unprecedented pace is taking place now. Our company is at the forefront of the wave of innovation in cell and gene therapy as well as digital health,” said Stefan Oelrich, Member of the Board of Management, Bayer AG and President of Bayer’s Pharmaceuticals Division. “We are driving this transformation and growing our promising development portfolio together with our partners. Our joint goal is to bring breakthrough treatments to patients and make healthcare systems more sustainable in the mid- and long-term.”
At its virtual Pharma Media Day, speakers from Bayer, its partners and leading experts demonstrated under the theme “Transforming Healthcare. Transforming Bayer” how the company is committed to transforming patient health by fulfilling its strategic ambition in
the areas of cell and gene therapy, digital health and by driving forward the company’s promising development portfolio.
Cell and Gene Therapy: Accelerating breakthrough innovation for patients
Cell and gene therapies offer for the first time the possibility to address the root cause of disease, providing options for conditions considered intractable or where the current standard of care only addresses symptoms to different degrees. Bayer’s increasing investments in the field are consolidating the company’s emerging leadership and confirm its strategic significance as a growth-driver for its pharmaceutical business.
Bayer has just established a new Cell and Gene Therapy Platform. This platform steers Bayer’s strategy in the area and orchestrates all activities along the value chain providing an innovation ecosystem for all partners, including BlueRock Therapeutics and Asklepios BioPharmaceutical (AskBio), two companies fully owned by Bayer but independently operated. Bayer’s development portfolio of cell and gene therapies already comprises seven advanced assets in different stages of clinical development. These are focused on multiple therapeutic areas with high unmet need, such as neurodegenerative, neuromuscular and cardiovascular indications, with leading programs in Pompe disease, Parkinson’s disease, hemophilia A, and congestive heart failure. With over fifteen preclinical assets in the cell and gene therapy field, the pipeline is expected to grow steadily year by year.
“Cell and gene therapies hold the promise to significantly impact patients’ lives by moving from treating symptoms to potentially curative approaches,” said Wolfram Carius, Executive VP and Head of Cell and Gene Therapy at Bayer. “Together with our partners, we want to accelerate innovation at its source and along the whole value chain to ensure a fast translation of science into therapies for patients who have no time to wait.”
BlueRock Therapeutics recently announced that the U.S. Food and Drug Administration (FDA) has cleared their Investigational New Drug application to proceed with a Phase I study in patients with advanced Parkinson’s disease. This will be the first trial in the United States to study pluripotent stem cell-derived dopaminergic neurons in patients with Parkinson’s disease and a big step forward for the stem cell field.
Digital Health: Empowering patients through Integrated Care
Digital healthcare offerings have become an important pillar of modern healthcare. The combination of conventional healthcare approaches with innovative digital technologies makes it possible to offer efficient solutions addressing the needs of a person in his/her specific environment. Bayer is developing Integrated Care concepts which offer individual
support of patients. This personalized approach addresses complex and interconnected health challenges within the individual circumstances.
Integrated Care is a key element of Bayer’s digital business strategy in pharma. In collaboration, Bayer and the digital health company Informed Data Systems Inc. (IDS/One Drop) are expanding their business based on IDS’s existing diabetes management platform. This solution was downloaded more than 3 million times. Together, the companies are now creating new health offerings to address the needs of patients in the areas of cardiovascular diseases, women’s health and oncology. Experts from both companies are jointly working on the first two modules, which are to become available within a year.
“By focusing on the individual patient, not their disease, Integrated Care is the path to truly inclusive and personalized healthcare,” said Jeanne Kehren, Senior VP of Digital & Commercial Innovation and Member of the Pharmaceuticals Executive Committee of Bayer AG. “We are determined to make Integrated Care solutions a major pillar of our company’s pharmaceutical business. Building on our expertise in the pharmaceutical sector, we can bridge the gap between tech and healthcare. In the next ten years, we expect digital health offerings to significantly contribute to our revenues.”
Growing a robust pipeline: New approaches for unmet medical needs
Bayer is continuing to build a strong development pipeline advancing more than 50 projects through the clinic with a focus on cardiovascular diseases, oncology and women’s health. The company highlighted two promising pipeline programs in mid-stage development demonstrating medical innovation at Bayer.
As an innovation leader in cardiovascular diseases with deep disease understanding and a long history of successful drug development, Bayer is particularly strong in the field of
Anticoagulation. Heart attack and stroke still represent a major health burden and new, more effective treatment options in thrombosis prevention are needed. The company is advancing a promising mid-stage program of Factor XI (FXI)-targeting compounds, a new class of anticoagulants, comprising of three investigational assets. A small molecule oral FXIa-inhibitor has commenced a Phase IIb program (PACIFIC), planning to enroll more than 4,000 patients in total. In addition, an anti-FXIa antibody and a FXI-ligand-conjugated antisense oligonucleotide (FXI-LICA), which Bayer is developing under exclusive license from IONIS Pharmaceuticals, have recently started Phase II trials, in patients with end stage kidney disease. FXI-pathway inhibition may offer protection from thromboembolic events without increased risk of bleeding. This may provide a treatment option to patients for whom currently no suitable therapeutic options are available.
With its P2X3 multi-indication program, Bayer highlighted another important candidate in mid-stage development. At Bayer, the promise of P2X3 antagonists was first identified for endometriosis within the company’s strategic research alliance with Evotec, a Germany based drug discovery and development company. Endometriosis is a clinical condition affecting approximately 10 percent of women in reproductive age, many of whom experience severe chronic pain with debilitating effects on their professional, personal and social lives. P2X3 also has a prominent role in several other medical conditions associated with pain and neurogenic hypersensitivity such as chronic cough, overactive bladder and neuropathic pain. Although these diseases are not life-threatening, they severely impact the quality of life for a very large number of patients – and P2X3 antagonists could potentially offer a new treatment approach and relief to these patients. For its development strategy, Bayer decided to explore a novel path in research and development pursuing not one but multiple possible indications early on and in parallel in the clinic. As of today, Bayer has entered Phase IIb clinical trials for refractory and/or unexplained chronic cough, with a trial in endometriosis soon to follow. In addition, Phase IIa clinical studies have commenced for overactive bladder and diabetic neuropathic pain.
“Our research in the fields of Factor XI inhibitors and P2X3 antagonists are just two promising examples of mid-stage programs that demonstrate our ongoing commitment to building and advancing a strong development pipeline,” said Stefan Oelrich. “Positioning Bayer as a leader in the highly dynamic space of healthcare innovation, we will continue to lead the field in bringing new solutions to patients who need them.”
At the same time, the company is also successfully delivering on its late-stage pipeline in the areas of oncology and cardiovascular disease including also a number of potential blockbuster products. In the area of oncology, for example, darolutamide (jointly developed with Orion Corporation), a differentiated treatment option that extends survival for men with non-metastatic castration-resistant prostate cancer who are at high risk for developing metastatic disease (nmCRPC), and shows a favorable safety profile. The product has received regulatory approval in several markets, including the U.S., the European Union (EU), Brazil, Canada and Japan. The Phase III study ARASENS in the indication of metastatic hormone sensitive prostate cancer (mHSPC) is expecting data read-out in 2021. Larotrectinib is a first-in-class precision oncology treatment designed to treat patients with solid tumors harboring a Neurotrophic Tyrosine Receptor Kinase (NTRK) gene fusion1. The product is approved in more than 40 countries, including the U.S. and countries of the EU. It was the first treatment in the EU to receive a tumor agnostic indication.
Finerenone is an investigational first-in-class treatment for patients with chronic kidney disease (CKD) and type 2 diabetes (T2D), a condition of high unmet medical need and limited treatment options. Finerenone has been submitted for marketing approval in the
US and in the EU based on Phase III data from the FIDELIO-DKD trial. The Phase III program with finerenone in CKD in T2D is the largest Phase III clinical trial program to date in CKD and T2D. It comprises two studies, evaluating the effect of finerenone versus placebo on top of standard of care on both renal and cardiovascular outcomes. The second Phase III trial in patients with CKD in T2D, FIGARO-DKD, is still ongoing. Vericiguat, which is being jointly developed with MSD (a tradename of Merck & Co., Inc., Kenilworth, NJ, USA), is currently under development for the treatment of patients with chronic heart failure and reduced ejection fraction (HFrEF). It could offer a specific mechanism of action to restore the functioning of a critical pathway, so far not addressed by current therapies. Vericiguat has been submitted for marketing authorization in the U.S., EU, Japan and China as well as multiple other countries. In July 2020, the FDA granted MSD’s application the status of priority review for the approval of vericiguat.
In the field of women’s healthcare, Bayer recently added a highly attractive asset to its development portfolio through the acquisition of KaNDy Therapeutics. BAY-342 (formerly
1 Larotrectinib is the first precision oncology therapeutic of its kind to treat adult and pediatric patients with solid tumors that display an NTRK gene fusion, who have a disease that is locally advanced, metastatic or where surgical resection is likely to result in severe morbidity, and who have no satisfactory treatment options.
NT-814) is a first in class, non-hormonal, once-daily, oral neurokinin-1,3 receptor antagonist for the treatment of vasomotor symptoms (hot flashes and night sweats) during menopause, planned to start Phase III development in 2021. End
About Cell and Gene Therapy
Emile Nuwaysir, CEO and President at BlueRock Therapeutics
The future of cellular medicine: Could stem cells engineer lost function?
Sheila Mikhail, Co-founder and CEO at Asklepios BioPharmaceutical
Advancing genomic medicine through AAV-based gene therapy
What are cell and gene therapy?
In cell therapy, functioning cells are delivered into a patient’s body in order to achieve a medicinal effect – to prevent, manage or cure a certain illness or to repair and regenerate damaged cells. These cells are either taken out of the patient’s body and given back to the same patient after treatment (in which case we talk about autologous therapies), or be standardized cells that can be used for multiple patients (allogeneic therapies). Cells can be either pluripotent (able to transform into all cell types of the body, with the exception of the extra-embryonic tissue like the placenta), multipotent (able to transform a limited number of cells in a particular lineage), or differentiated (a fixed cell type). The kind of cells introduced depends on which disease they are supposed to address.
Gene therapy aims to treat or cure a disease by delivering genetic material into a patient’s cells. This way, cells which have been lacking the correct instructions to work properly receive the genetic information that will allow them to restore their function. The genetic information delivered to the person’s cells (either by adding a missing gene sequence or correcting or deleting a faulty one) changes how these cells produce proteins, for example by reducing the production of proteins that are causing a disease or producing new proteins that have been missing.
Why do cell and gene therapy matter?
Genetic diseases are caused by faulty genes that are present in almost every cell in the body of a patient suffering from the disease, making them nearly impossible to tackle via traditional medicines. For patients suffering from genetic disorders, this meant that treatment was limited to alleviating the symptoms that came with their condition. Cell and gene therapies have the potential to shift the paradigm of disease treatment to cure – with potentially enormous effects for patients’ lives.
Gene therapy has already demonstrated the potential to restore blood clotting in people with hemophilia, restore the visual cycle in patients with Leber’s congenital amaurosis (a rare form of inherited blindness) and to improve outcomes with regards to survival and motor function in babies suffering from spinal muscular atrophy.
Cell therapy, likewise, offers a wide variety of applications: approaches like blood transfusions and the regeneration of bone marrow via stem cells already have a long history of success. Induced pluripotent stem cells (or iPSCs) are uncovering promising new avenues in stem cell therapy, such as the restoration of motor function in patients suffering from Parkinson’s Disease or the regeneration of heart tissue damaged after myocardial infarction.
Cell and Gene Therapy at Bayer
Bayer is strongly committed to leading the field of cell and gene therapies, an area that represents the next wave of medical innovation and an attractive growth opportunity.
In order to consolidate this leadership, Bayer is strengthening its internal capabilities while at the same time, pursuing external strategic collaborations, technology acquisitions and licensing. The goal is to build robust platforms with broad application across different therapeutic areas. Bayer’s newly established Cell and Gene Therapy Platform strategically steers all of the efforts in the area, coordinating the activities of the different partners that integrate the Platform, such as BlueRock Therapeutics and Asklepios BioPharmaceutical (AskBio).
In 2016, Bayer and Versant Ventures established BlueRock Therapeutics, which was fully acquired by Bayer in 2019. BlueRock Therapeutics is an engineered cell therapy company working to develop regenerative medicines for intractable diseases. BlueRock’s technology seeks to restore tissue function in diseases with significant cell loss and diminished self repair potential, with an initial focus on neurological and cardiovascular conditions, among others.
In 2020, Bayer acquired AskBio, a biopharmaceutical company specialized in the research, development and manufacturing of gene therapies across different therapeutic areas.
AskBio’s development portfolio includes investigational pre-clinical and clinical stage candidates for the treatment of neuromuscular, central nervous system, cardiovascular and metabolic diseases.
Bayer’s development portfolio of cell and gene therapies already comprises seven advanced assets in different stages of clinical development, with leading programs in Pompe disease, Parkinson’s disease, hemophilia A, and congestive heart failure. With over fifteen preclinical assets, the pipeline is expected to grow steadily year by year.
Dr. Nuria Aiguabella Font
+49 30 468193131
About Digital Health & Integrated Care
Jeff Dachis, Founder & CEO of Informed Data Systems Inc.(One Drop)
How data-driven solutions deliver true patient-centricity
Prof. Dr. Martin C. Hirsch, Philipps University Marburg
AI in Medicine: Why should we trust the ‘black box’?
What is Digital Health?
In recent years, Digital Health has grown to become an important pillar of modern healthcare. The combination of conventional healthcare approaches with digital technologies makes it possible to better help patients by offering solutions that are more efficient and increasingly tailored to their individual circumstances and able to fit with their lives.
Industry experts are expecting digital products and services to make up a market share of 12 percent within the healthcare sector by 2025, with worldwide spending on digital health going up to EUR 979 billion.1
What is Integrated Care?
Integrated Care is an application of digital health that aims at developing coordinated concepts of care, supporting patients throughout their lives, accounting for multi-morbidity, and offering the support they need, whenever and wherever.
Integrated Care aims to empower the patient. Digital solutions allow them to track and manage their own health in every moment of their daily lives, taking the concept of care beyond the doctor’s office into the realm of everyday life. Using artificial intelligence, machine learning, and vast amounts of data, they enable people to gain control of their health through predictive, proactive and actionable insights. With Integrated Care, healthcare will move from treating (chronic) diseases towards managing one’s health and staying healthy.
Why does it matter?
Medical conditions never exist in a vacuum. Patients suffering from a disease may have co morbidities with other illnesses, to the effect that the different conditions influence and 1 Morris Hosseini, Thilo Kaltenbach, Ulrich Kleipaß, Karsten Neumann, Oliver Rong:
Future of Health 2 – The Rise of Healthcare Platforms
impact each other. Beyond that, individual circumstances influence disease progression and the ability to implement treatment and advice – every health journey is unique.
This is a reality that the pharmaceutical industry’s traditional approach of “single issue” treatment has had difficulties addressing in the past. The holistic approach of Integrated Care puts the patient, not the disease, front and center in the healthcare process, allowing support offerings to be tailored to fit each patient’s unique needs.
Through this approach, we are changing the perception on health and disease, from discrete observations during interactions with the healthcare system to a continuous description. This will create new perspectives for our approaches to treatments.
Integrated Care at Bayer
Bayer Pharma is aiming to be a key player in digital healthcare, building on its expertise and scientific know-how to create solutions and enabling access, thereby helping patients and making healthcare systems more efficient.
Integrated Care is a key element of Bayer Pharma’s digital business strategy. Bayer and the digital health company Informed Data Systems, Inc. (One Drop) are building on One Drop’s existing diabetes management platform, which has been downloaded more than 3 million times since 2016. Building on One Drop, Bayer Pharma and IDS will jointly develop and evolve an integrated digital health platform offering solutions that help patients in the areas of Cardio-Renal Diseases, Women’s Health and Oncology. Experts from both companies are jointly working on the first two modules, which are expected to be released within a year.
About FXI-Targeting Drugs
So-Young Kim, MD, Head of Thrombosis and Vascular Diseases, Bayer
Factor XI: Targeting a paradigm shift in anticoagulation
What are Factor XI-targeting drugs?
Factor XI-targeting drugs are a new class of drug compounds currently under development primarily in the area of anticoagulation that function by inhibiting Factor XI. Factor XI is a naturally occurring enzyme that is part of the coagulation cascade which, as evidence suggests, plays a key role in the formation of pathological blood clots, and consequently, thrombosis.
The significance of Factor XI inhibition in fighting thrombosis was discovered by studying ethnic groups who have a lower risk of suffering from strokes and blood clots. In this process, it was found that Ashkenazi Jews show an above average presence of inherited FXI deficiency. While FXI deficiency can be associated with a mild tendency to bleed, carriers do not usually suffer from strong spontaneous bleeding events. At the same time, however, people with FXI deficiency have lower risks of deep-vein thrombosis and stroke than the general population, showing that inhibiting the production of Factor XI might be a promising way to prevent the formation of blood clots while maintaining normal hemostasis.
Why does it matter?
Anticoagulants have been used in the prevention and treatment of thrombosis since the early 20th century. Early anticoagulants necessitated precise coagulation monitoring, making out-of-hospital therapies difficult. And while modern anticoagulants have managed to overcome this to a certain extent, a certain risk of bleeding may remain, especially in patients with comorbidities.
This leads to some eligible patients either not receiving antithrombotic therapy or lower-than ideal doses of anticoagulants, leaving them at higher risk of strokes. In addition, certain patient groups are not eligible for the current anticoagulation treatments available. Therefore, there remains a medical need for a novel class of anticoagulants. Factor XI inhibition could potentially offer a novel safety and efficacy profile that would make it possible to treat millions of cardiovascular patients who are currently underserved.
The Factor XI program at Bayer
Bayer is currently exploring novel approaches targeting Factor XI-pathway inhibition with three investigational assets are in Phase II clinical development: a small molecule FXI(a) – inhibitor and an anti-FXI(a) antibody (osocimab), which are both targeting the activated form of coagulation factor XI (FXIa), as well as a FXI-ligand-conjugated antisense oligonucleotide (FXI-LICA, in-licensed from IONIS Pharmaceuticals). For the small molecule FXIa-inhibitor, Bayer initiated a comprehensive Phase IIb program (PACIFIC) in Q1/2020 to evaluate the safety and efficacy of the candidate in three distinct indications: stroke prevention in patients with atrial fibrillation, secondary stroke prevention after an acute non-cardioembolic stroke, and prevention of major adverse cardiac events after an acute myocardial infarction. Under the name PACIFIC, the program plans to enroll more than 4.000 patients in total. For osocimab and the FXI-LICA, Phase IIb studies (CONVERT & RE-THINC) in end stage kidney disease patients were recently started.
+49 30 468-192038
About P2X3 Antagonists
Oliver Martin Fischer, Principal Scientist Reproductive Health, Bayer
P2X3: Driving multi-indication programs forward
What are P2X3 Antagonists?
P2X3 is a protein, which is mainly expressed on sensory nerve fibers. It is one of many receptors activating afferent nerve signaling, meaning axonal projections that arrive at particular regions of the brain in response to internal and external stimuli. Studies have shown that P2X3 plays an important role as natural mediator of pain and nerve hypersensitivity in peripheral pain responses, and it functions as inducer of neurogenic inflammation. Under normal circumstances, activity of P2X3 signaling is modest, whereas under conditions of chronic inflammation, signaling activity through P2X3 is significantly enhanced. As a result, chronic inflammation renders peripheral nerve fibers hypersensitive, to the point where they are activated without external stimuli, trapping patients in a vicious circle of pain and inflammation.
P2X3 antagonists block the receptor with the aim to decrease peripheral nerve fiber sensitivity. At Bayer, the class of P2X3 antagonists as potential new treatment option for patients affected by conditions with nerve hypersensitivity and pain was first identified within the company’s strategic research alliance with Evotec SE in connection to their joint endometriosis research. But P2X3 also seems involved in several other diseases characterized by painful neurogenic hypersensitivity including refractory or unexplained chronic cough, overactive bladder and neuropathic pain.
Why does it matter?
Worldwide, approximately 10 percent of all women in reproductive age suffer from endometriosis, a condition causing uterine cells grow outside of the uterine cavity, leading to lesions in the lower abdomen. Women with endometriosis often experience severe chronic pain that has debilitating effects on their professional, personal and social lives; infertility is another recognized symptom. Medical treatments are associated with limitations and in many cases, surgical removal of the lesions is necessary to reduce symptoms. There is substantial need for novel medical treatment options that are non-hormonal and effective and suitable for long-term use. Refractory or unexplained chronic cough (RUCC) affects 1-5 percent of all people worldwide. RUCC has a debilitating effect on patients’ lives, causing them to cough between 10 to 100 times per hour without any external trigger, with phases often lasting for months or even years. Treatment options available for chronic cough are limited, with no treatment approved in the indication RUCC. Overactive bladder (OAB) is a highly prevalent chronic condition that affects approximately 12 percent of adults worldwide
and becomes more frequent in the elderly population. For many people living with OAB, their symptoms have a direct negative effect in most activities outside of their homes, and
patients commonly experience anxiety, depression and sleep disturbances. Neuropathic
pain is a severe pain condition that is caused by damaged nerves and is often long-lasting. It is present in 7-10 percent of the general population. Chronic neuropathic pain is more
challenging to treat than other types of pain and, thus, is often poorly managed. A high
unmet need remains for more efficacious treatment with better safety and tolerability.
Although these diseases are not life-threatening, they severely impact the quality of life for a very large number of patients. P2X3 antagonists could potentially offer new treatment
approach and relief to these patients.
The P2X3 multi-indication program at Bayer
Based on an in-depth biochemical understanding of the role of P2X3 in chronic inflammation, Bayer decided to explore a novel path for its clinical development strategy: pursuing not one but multiple possible indications in parallel early on, although this may also lead to
indications outside Bayer’s current strategic therapeutic area of focus.
The company’s investigational P2X3 receptor antagonist is currently being evaluated in a Phase IIb dose-finding study in patients with RUCC, which will enrol more than 200 patients. Previously, in a Phase IIa study, proof-of-concept was achieved and all study endpoints regarding safety and efficacy were met, including observation of only low rates of mild taste related adverse events. In the indication endometriosis-related pain, another Phase IIb clinical study is expected to start soon. Two clinical Phase IIa proof-of-concept studies have recently been initiated in the indication OAB and diabetic neuropathic pain and are ongoing.
What began as a research project trying to find a better treatment for just one condition, has transformed into a multi-indication program that now has the potential to provide meaningful therapeutic options for patients suffering from a series of similar yet very different diseases.
Dr. Julia Schulze