Excellence in research & development
Core Growth Areas
Biogen has a long history in neurology and has built up substantial core competencies in the area. It is our belief that no other area of medicine holds as much promise with as much need as neuroscience. The opportunity space is vast and the time is right. We aim to be the leader in neuroscience, by developing transformational therapies to address what we believe are becoming the world’s most significant unmet medical needs.
To that end, and recognizing that as a therapeutic area and field of biomedicine, neuroscience is large with many intersecting disciplines, our strategy is to focus on four core areas for growth and four emerging areas for growth.
MS & Neuroimmunology
Multiple sclerosis (MS) affects approximately 2.5 million people worldwide and is an unpredictable, often disabling disease of the central nervous system. Symptoms can vary over time and from person to person and may include problems with balance and walking, hand function, numbness or other sensory changes, visual impairment, bladder and bowel symptoms as well as issues with memory and concentration and may impact a patient’s ability to work and function independently.
We have been deeply committed to understanding and treating MS for decades. Biogen has a unique portfolio of approved drugs to treat MS, ranging from different disease modifying treatments differentiated by route of administration, mechanism of action, and relative efficacy to address the inflammatory components of the disease, to symptomatic treatments. The need for continuing to seek new ways of treating MS is as important as ever.
We are undertaking a number of approaches to further our understanding of the disease and how to treat it. These include applying human genetics to understand the basis of disease progression, investigating new approaches to repair damaged nerves in the central nervous system with the goal of improving pre-existing disability, and looking at ways of treating progressive forms of MS. We also have an active research program into neuroinflammation, particularly studying the resident central nervous system immune cells called microglia and how they contribute to inflammation and pathology across multiple neurological diseases.
We welcome collaborations with academic and industry partners around the world in the pursuit of transformative therapies in MS and neuroimmunology.
Learn more about Biogen in MS
Our heritage in neurology is built on years of research into the most complex neurodegenerative diseases and we bring this expertise and experience to our work in Alzheimer’s disease and dementia. Our strategically diverse portfolio of investigational products represents the latest advances in Alzheimer’s disease, including aducanumab, the first investigational treatment to reduce amyloid plaque that has shown evidence of slowing cognitive decline, as well as additional experimental approaches targeting amyloid and tau pathology.
We are developing and incorporating advanced imaging and biomarker technologies into our programs to improve the ability to accurately diagnose this disease as early as possible. Our Phase 1b study of aducanumab was the first to confirm Alzheimer’s disease by PET imaging in all enrolled patients (Sevigny et al 2016).
Alzheimer’s disease and other dementias are complex and will likely require multiple therapeutic approaches. We continue to research underlying mechanisms and to identify new targets to address different pathways including post-translational modification of tau, synaptic plasticity, and neuroinflammation. Our efforts cross many scientific disciplines. We are capitalizing on the advances in molecular and cellular biology, and connecting them with human genetic discoveries.
Along with building a team of expert scientists, clinicians, and technologists, we are also pursuing external collaborations to advance our Alzheimer’s disease programs. Collaboration is critical to our efforts and our external collaborations ensure our scientific teams and those from the world’s leading academic institutions are connected.
Our work in movement disorders builds on our neuroscience strengths. We have built a preclinical and early clinical portfolio around Parkinson’s disease (PD) directed at targeting core disease genetics and pathology. Our initial programs target α-synuclein, the best validated PD target, through distinct approaches. Future programs aim to broaden the range of targets and modalities for PD, build a strong suite of disease-related biomarkers, and continue our productive interactions with patient associations and foundations who lead the way in PD research.
We aim to leverage our research and clinical experience in PD to bring new therapies to patients suffering from this and other movement disorders.
Our efforts in neuromuscular disorders are focused on two main areas: spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS).
We have brought forward the first and only approved therapy for SMA, and our scientists continue to work toward new therapeutics for SMA patients, including a gene therapy approach in collaboration with the University of Pennsylvania.
Despite the existence of two FDA-approved drugs, there are still no potent disease-modifying therapies for ALS. Our most advanced programs focus on the familial, inherited forms of ALS that collectively represent ~10% of all patients, and use antisense oligonucleotides to reduce the levels of the disease-triggering genes. In addition to the hoped-for benefit to patients, these trials will allow us to evaluate new clinical endpoints and biomarkers developed at Biogen. We believe that smaller, quicker clinical trials will be particularly important as we take on the most frequent, sporadic cases of the disease. To take on this challenge, we have built a preclinical pipeline for high-throughput evaluation of a wide range of therapeutic targets and modalities.
Emerging Growth Areas
Our emerging growth areas derive from our deep expertise in our core growth areas. These areas of focus aim to create synergies and leverage our scientific expertise from adjacent areas.
Chronic pain afflicts 10-20% of the world’s population (Treede et al, 2015), and is a leading cause of long-term disability. It exacts substantial psychological and financial costs on sufferers and society at large. Current medications, including prescription opioids, are not always effective and have significant shortcomings as highlighted by the ongoing crisis of overuse and addiction. Therefore, the need for medications targeting pain with novel and distinct mechanisms is as great as ever.
Our approach to pain therapeutics is guided by several principles to improve probability of success. One is to apply insights from human genetics, selecting drug targets and pathways directly implicated in excessive or absent pain in rare genetic conditions. Our development of inhibitors to Nav1.7, a sodium channel expressed in pain circuits, exemplifies this approach, and is currently in clinical trials. Another approach is to initially test new drug candidates in carefully defined patient populations with severe pain conditions such as trigeminal neuralgia. We are also excited to explore the possibility of combining multiple approaches for engaging a drug target: small molecules, antibodies, peptides, or other modalities. We actively pursue collaborations with academic and industry partners in the pursuit of innovative new pain therapies.
The retina, the light-sensitive innermost layer of the eye, is an extension of the central nervous system (CNS) developmentally, anatomically and functionally. Our extensive expertise in disorders of the CNS has been instrumental in the decision to pursue ophthalmology as a therapeutic area and shaping Biogen’s ophthalmology portfolio.
In collaboration with our partner AGTC, we are engaged in two Phase I/II gene therapy programs in X-linked retinoschisis (XLRS) and X-linked retinitis pigmentosa (XLRP), two rare inherited retinal disorders. We also continue to explore several modalities beyond gene therapy for engaging drug targets, including antibodies, peptides, and small molecules. We have expanded our discovery efforts with other innovative industry and academic partnerships in the pursuit of delivering transformative therapies to patients with vision loss caused by disorders of the retina and the optic nerve.
Almost 1 in 5, or 43.4 million, adults in the US experience psychiatric illness in a given year, with even higher rates seen in neurological, neurodegenerative and general medical settings. These symptoms result in diminished qualify of life, productivity and life expectancy, and as a result place substantial burden on patients, families, and the broader healthcare system. Psychiatric symptoms and cognitive impairment are also frequent in the context of neurodegenerative diseases like Alzheimer’s and Parkinson’s disease and represent an unmet need.
Building on recent advances in genetics, cognitive neuroscience, neuroimaging and pharmacology, Biogen aims to leverage its expertise and track record in neurological diseases to deliver novel neuropsychiatric therapeutics. Our access to a range of therapeutic modalities, including gene therapy, biologics, antisense oligonucleotides and small molecules will allow Biogen to bring new options to patients suffering from neuropsychiatric and neurodevelopmental disorders. Biogen is actively pursuing partnerships and collaborations with academic and industry groups to develop innovative solutions for these patients.
In acute neurology, we are focused on discovering and developing new medicines to treat acute brain injury. Acute brain injury, including stroke, traumatic brain injury, and seizures are leading causes of permanent disability in our society, and most patients who sustain them do not currently receive disease modifying therapies. This focus area builds on our core expertise in areas such as neuroinflammation, blood-brain barrier integrity and neurorepair to translate advances in these areas of biology into new treatments for patients. We have an innovative portfolio of compounds that target peripheral immune cell infiltration, brain edema, glial cell activation, and cell death pathways, which have the potential to transform clinical care paradigms in acute brain injury.
Past efforts to develop therapies in acute brain injuries have often focused on targets that were poorly validated and without biomarkers to understand their clinical pharmacology or provide proof of biology in the clinic. Within this focus area, we have advanced novel treatments with well-established pharmacologies on defined central nervous system (CNS[SM1] ) targets that have demonstrated meaningful benefits for patients in early trials. We will continue to place a rigorous emphasis on target selection, patient enrichment strategies, and advances in translational medicine as we build partnerships with other centers of excellence to advance new medicines for patients with this frequently devastating class of disorders.
Our core research platforms are designed for predicting drug concentrations in blood and tissues such as the central nervous system (CNS) using physiologic based pharmacokinetic modeling approaches, and linking these concentrations to drug effects using biomarker, imaging, safety and clinical endpoints. These platforms are built to support key drug modalities used at Biogen including small molecules, biologics, antisense oligonucleotides and gene therapy.
Biomarkers & Translation Biology
Biomarkers are indicators of normal or pathogenic biological processes, or pharmacologic response to a drug or other therapeutic intervention. Our expert team of biomarker scientists are focused on discovering, validating, and applying novel assays, medical imaging, and other cutting-edge technologies to measure biomarkers that yield insights into the effects of our drugs. We focus on answering key questions in patients to improve the probability of our experimental drugs becoming successful medicines, such as: which patients are most likely to respond? What is the optimal drug dose and dosing interval? Does the drug treatment impact disease-related biology?
We work within our laboratories and with external collaborators to discover and validate novel assays, imaging probes, data analysis methods, and technologies across Biogen’s disease areas of interest. We collaborate throughout the world with preclinical and clinical centers of excellence in biomarker research, and access leading technologies through partnerships, licensing and acquisitions. We are industry pioneers in the use of biomarkers for assessing drug safety and efficacy in MS and SMA, and are breaking new ground in clinical trials of neurodegenerative diseases through our innovative use of positron emission tomography (PET) and magnetic resonance imaging (MRI) to select patients, monitor safety, and assess the biological effects of treatment. Our expertise in biomarker science combined with a deep knowledge of drug discovery and development ensures appropriate context of use.
Drug Metabolism & Pharmacokinetics (DMPK)
Drug Metabolism & Pharmacokinetics (DMPK) enables the discovery and development of safe and effective medicines by providing insight into the mechanisms of drug absorption, distribution, metabolism, and excretion (ADME). DMPK assesses drug-drug interaction potential, pharmacokinetics and central nervous system (CNS) distribution, and translational pharmacokinetic and pharmacodynamic modeling across various therapeutic modalities of Biogen’s portfolio.
We rely on industry-leading experimental and mathematical models to assess the biochemical fate of lead molecules and clinical candidates, including the contribution of metabolic enzymes towards ADME and identification of metabolites. We excel in non-regulatory and regulatory preclinical and clinical bioanalysis, providing the critical link of exposure to pharmacology and safety. This work utilizes specialized CNS delivery and sampling techniques to assess distribution kinetics via continuous collection of cerebrospinal fluid (CSF) and intrathecal dosing. We implement quantitative mechanism-based models describing the relationship between target modulation and pathway physiology to support the pharmacodynamic-driven clinical dose and schedule.
ADME, PK, PD and Clinical Pharmacology
Once our programs transition from research to early clinical development, clinical pharmacology and pharmacometrics aims to determine the right dose of the right molecule for the right patient across all of our therapeutic areas throughout the drug development spectrum. This involves designing, analyzing, and interpreting results from pre-clinical and clinical studies. We build and validate mathematical models to characterize the drug disposition in the body over time (i.e., pharmacokinetics), and to link drug levels in blood/tissues with drug effects on biomarkers, efficacy, and safety (i.e., pharmacodynamics).
Given our focus in neuroscience, our core research platforms are designed to predict drug concentrations in blood, plasma, and tissues in the central nervous system using physiologic based pharmacokinetic modeling approaches. These platforms are built to support key drug modalities including small molecules, biologics, antisense oligonucleotides and gene therapy. We also collaborate with internal and external partners to build translational and drug-disease models to better characterize and predict drug effects in the body (i.e., PET imaging, CSF measurements) and link these early biomarkers to patient outcome.
Preclinical safety focuses on the non-clinical safety assessment of our small molecule, biologics, anti-sense oligonucleotide and gene therapy candidates to enable the selection, development and marketing of safe and efficacious medicines to improve the lives of patients. Our expert team of toxicologists, pathologists, and study managers begin their project involvement at an early stage of drug discovery and carry these responsibilities through all phases of clinical development and marketed products.
It is imperative to characterize and understand the safety profile of our drug candidates, which enables effective development strategies and decision making in our programs. We do this by initially conducting screening studies to select and advance safe targets and molecules from discovery into development, followed by continued effective non-clinical safety assessment studies to support clinical development and ultimately, the commercialization of our therapeutic candidates.
Biogen discovers and develops therapeutics in multiple drug modalities, including small molecules, biologics, anti-sense oligonucleotides, and gene therapy. The breadth of our capabilities is a result of internal expertise as well as strategic collaborations with talented partners.
Small molecule therapeutics can often be taken as an oral pill, distributing into cells and tissues, including the brain, differently than other therapeutic modalities.
Through a series of rational design cycles, our work in small molecules aims to incrementally improve the small molecule’s properties, to enable it to work as a medicine. We screen libraries to find starting points and model how these compounds might interact with their targets using a variety of computer-aided drug design approaches. Using medicinal chemistry strategies in design and synthesis, we invent these molecules and then test them for their potency, ADMET (absorption, distribution, metabolism, excretion, toxicity) and selectivity profiles against the target of interest. We use biophysics techniques such as high-resolution X-ray crystallography, Nuclear Magnetic Resonance and Surface Plasmon Resonance to observe whether the small molecules are binding in the way we expected. In addition, we design key tools in our small molecule work that are chemical probes which enable us to identify essential attributes of the parent molecules such as what proteins or RNA/DNA they bind to, or which compartment in the cell or tissue they exert their biological effects in vitro and in vivo. Chemical probes are indispensable not only for target identification and understanding mechanism of action but also to facilitate quantification of target engagement in vivo.
The process of rational design results in small molecule candidates that have appropriate characteristics to be effective in pharmacodynamic models that mimic human disease, and are safe for patients.
Therapeutic proteins, also referred to as biologics, differ dramatically from traditional small molecule drugs. Biologics, which include monoclonal antibodies, growth factors, cytokines, enzymes and many other types of proteins, are often as much as a thousand times the size of small molecule drugs, and are manufactured in living cells rather than through chemical synthesis. Although this type of drug is much more complicated to make and characterize, using biologics allows scientists to attack serious disease in ways that might not be possible with other technologies. Antibodies (and antibody-like proteins) have become the most common type of biologic because of the exquisite specificity and long duration of action of this type of molecule.
The biotechnology industry was built around the development of protein therapeutics beginning in the late 1970s. As one of the oldest independent biotechnology companies in the world, Biogen scientists have contributed to the development many of these medicines, including recombinant interferons, antibodies and several experimental neurology treatments in our clinical development portfolio such as aducanumab and opicinumab.
As we look to the future, our scientists continue to explore new and innovative ways to apply the power of protein therapeutics to transform the treatment of neurologic disease.
Anti-Sense Oligonucleotides (ASOs)
The approval of the first and only treatment for spinal muscular atrophy as an antisense oligonucleotide (ASO) spearheaded Biogen’s commitment to development of ASOs as a newly emerging therapeutic modality to treat severe neurological diseases, working with our collaboration partner Ionis Pharmaceuticals.
ASOs are synthetic single stranded nucleic acids consisting of 8-50 nucleotides which bind to RNA to interfere with target gene expression. ASOs utilize several distinct mechanisms to alter RNA and either restore desired protein expression or reduce and modify a toxic protein, enabling them to be used as a powerful modality to establish convincing proof of biological function. Hence ASOs are a promising therapeutic modality in the treatment of several neurodegenerative disorders to prevent disease onset or arrest disease progression.
We are committed to enhancing knowledge of various facets of the ASO platform and to be world-class in quantitative understanding of human pharmacokinetic/pharmacodynamic models by utilizing learnings of physiologic-based distribution in the central nervous system (CNS) following intrathecal delivery. We are passionate about developing transformational therapies with innovative science, dedicated partnerships and patient-focused implementation.
Gene therapy represents the newest addition to Biogen’s suite of therapeutic modalities. By introducing nucleic acids into a patient’s cells, this method provides the potential to repair, inhibit or replace the defective genes that lead to disease. To do this, viruses are engineered to safely deliver the therapeutic cargo to target cell types. Gene therapy expands our potential to treat previously intractable diseases by capitalizing on recent advances in our understanding of human genetics. Through internal efforts and in collaboration with leaders in academia and industry, we are working to advance gene therapy technologies, focusing on the development of therapeutic approaches targeting diseases of the eye and the central nervous system.