Scientific Expertise

Neurological diseases are the leading cause of disability and second leading cause of death worldwide. The prevalence of these devastating diseases and the societal burden are growing as a result of the aging population globally.

At Biogen, we believe that the pathways of neurological diseases are interrelated, and so are the potential approaches for treating them. Our deep understanding in multiple sclerosis (MS) has given us insight into other disease areas of the central nervous system (CNS), where common pathophysiological processes and disease characteristics may be leveraged in other areas of research and development. For example, we’re researching myelin repair for progressive MS, which may have additional potential in Alzheimer’s disease (AD), Parkinson’s disease (PD), stroke, pain, and amyotrophic lateral sclerosis (ALS).

We are prioritizing our resources on what we believe are the most promising programs and funded research and development expenditures of $2.6 billion in 2018.

 

Core Growth Areas

 

Multiple Sclerosis & Neuroimmunology

Our deep commitment to understanding and treating multiple sclerosis (MS) is evidenced by a track record of successes and innovation in the treatment of that disease. 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 variety 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 in neuroinflammation, studying its pathology across multiple neurological diseases.

Alzheimer's Disease & Dementia

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 Alzheimer’s disease and dementia therapeutic area. Our strategically diverse portfolio of investigational products includes several assets targeting early-stage Alzheimer’s disease (AD).

We are developing and incorporating advanced imaging and biomarker technologies into our programs as we aim to improve the ability to accurately diagnose this disease as early as possible.

AD and other dementias are complex and will likely require multiple therapeutic approaches. We continue to research underlying mechanisms and to identify new potential 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 AD 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.

PARKINSON’S DISEASE & RELATED MOVEMENT DISORDERS

Our work in movement disorders builds on our neuroscience strengths. We currently have a preclinical and clinical portfolio around Parkinson’s disease (PD) and progressive supranuclear palsy (PSP) targeting core disease genetics and pathology.

In PD, our initial programs target α-synuclein, a 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.

PSP, an atypical Parkinsonism, is a rare adult-onset neurodegenerative disease that is believed to be caused by the accumulation of an abnormal form of tau in the brain. Our PSP program’s focus is to target and remove extracellular tau which may reduce the spreading of abnormal tau and potentially slow the progression of the disease.

NEUROMUSCULAR 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 approved therapy for SMA, and our scientists continue to work toward new potential therapeutics for SMA patients.

Approximately 90-95 percent of ALS cases present without a family history and are characterized as sporadic. The remaining approximately 5-10 percent are caused by familial, inherited forms of ALS. Despite the existence of two FDA-approved drugs, there are still no potent disease-modifying therapies for ALS. Our most advanced investigational programs, which focus on the familial, inherited forms of ALS, use antisense oligonucleotides to reduce the levels of the disease-triggering proteins. 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 evaluation of a wide range of therapeutic targets and modalities for ALS.

 

Emerging Growth Areas

 

ACUTE NEUROLOGY

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. In addition to our core expertise in areas such as neuroinflammation, blood-brain barrier integrity, and neurorepair, 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.

Neurocognitive Disorders

Almost 1 in 5, or 43.4 million, adults in the U.S. 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. 

Building on recent advances in genetics, cognitive neuroscience, neuroimaging, and pharmacology, as well as our access to a range of therapeutic modalities, Biogen aims to leverage its expertise in neurological diseases to deliver novel therapeutics.

Pain

Chronic pain afflicts 10-20 percent of the world’s population, and is a leading cause of long-term disability. It exacts substantial psychological and financial costs on sufferers and society at large. 

Our approach to pain therapeutics is guided by several principles to improve probability of success, including selecting drug targets and pathways in rare genetic conditions, testing new drug candidates in patient populations with severe pain conditions, and exploring the possibility of combining multiple approaches for engaging a drug target. Our development of inhibitors to Nav1.7, a sodium channel expressed in pain circuits, exemplifies this approach, and is currently in clinical trials. 

OPHTHALMOLOGY

The retina is an extension of the central nervous system (CNS) developmentally, anatomically, and functionally. Biogen’s ophthalmology portfolio bolsters our pipeline across complementary modalities while leveraging our extensive expertise in disorders of the CNS.

With our acquisition of Nightstar Therapeutics, we are engaged in early clinical gene therapy programs for two rare inherited retinal disorders: choroideremia (CHM) and X-linked retinitis pigmentosa (XLRP). We also continue to explore several modalities beyond gene therapy for engaging drug targets, and have expanded our discovery efforts with other innovative industry and academic collaborations in the pursuit of delivering transformative therapies to patients with vision loss caused by disorders of the retina and the optic nerve.

 

Therapeutic Adjacencies

We have several ongoing clinical programs that aim to advance research in other therapeutic conditions. As we advance our multi-franchise portfolio, we are excited by the possibility of pioneering new scientific breakthroughs and bringing new potential treatment options to patients in need.

 

Lupus & Pulmonary Fibrosis

Lupus is a chronic inflammatory disease that occurs when the body’s own immune system mistakenly attacks healthy tissue in the brain and other organs including the skin, joints, and kidneys. It is a difficult disease to diagnose because it resembles several other conditions. We’re studying potential therapeutics for cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE).

Pulmonary fibrosis is a disease in which lung tissue becomes thickened and stiff due to scarring. The formation of scar tissue is called fibrosis. As the disease progresses, it becomes harder for the lungs to work properly and the body cannot get the oxygen it needs. This debilitating disease is almost always fatal. We are studying a potential therapy for the most common type of this condition – idiopathic pulmonary fibrosis.

 

Through the use of our core platforms and modalities, Biogen is bringing new scientific understanding to diseases for which there are no adequate treatments. These research platforms are built to support key drug modalities used at Biogen including small molecules, biologics, antisense oligonucleotides, and gene therapy.  

 

Platforms

Our core research platforms are designed to predict drug concentrations in blood and tissues using physiologic based pharmacokinetic modeling approaches, and linking these concentrations to drug effects using biomarker, imaging, safety, and clinical endpoints.

 

BIOMARKERS & TRANSLATIONAL BIOLOGY

Biomarkers are indicators of normal or pathogenic biological processes, or pharmacologic response to a drug or other therapeutic intervention. 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. We employ optical coherence tomography (OCT) in ophthalmology studies to assess biological effects of treatments in our clinical trials.

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. Our expertise in biomarker science combined with a deep knowledge of drug discovery and development ensures appropriate context of use.

DRUG METABOLISM & PHARMACOKINETICS

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). 

We utilize industry-leading experimental and mathematical models to assess the biochemical fate of lead molecules and clinical candidates and understand how they break down and are absorbed, distributed, metabolized, and excreted by the body. Specific to neuroscience, we enhance our analyses using specialized CNS-targeted delivery and continuous cerebrospinal fluid (CSF) sampling techniques to assess distribution kinetics, giving us critical pharmacodynamic information to help determine optimal dosing and scheduling.  

CLINICAL PHARMACOLOGY & PHARMACOMETRICS 

After defining the behavior of a drug candidate in various preclinical models, we then apply that information in the human context, using clinical pharmacology and pharmacometrics 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 CNS using physiologic based pharmacokinetic modeling approaches, with translational and drug-disease models to better characterize and predict drug effects throughout the nervous system, (i.e., PET imaging, CSF measurements) and link these early biomarkers to patient outcome. 

SAFETY SCIENCES

We use extensive screening tests to select and advance safe targets and molecules from discovery into development. 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.  


Modalities 

Biogen discovers and develops therapeutics in multiple drug modalities, including small molecules, biologics, antisense oligonucleotides, and gene therapy. 

 

SMALL MOLECULES

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 a drug candidate’s physicochemical properties, to enable it to work as a medicine. This process begins with screening vast libraries of molecules to find starting points and model how these compounds might interact with their targets. We utilize medicinal chemistry and synthesis, testing molecules in functional assays that replicate the target and tell us whether the small molecules are binding in the way we expected or if they are having off-target effects.  

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.

PROTEIN THERAPEUTICS

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.

As one of the oldest independent biotechnology companies in the world, Biogen scientists have contributed to the development of many of these medicines, including recombinant interferons, antibodies, and several experimental neurology treatments in our clinical development portfolio such as opicinumab.

ANTISENSE OLIGONUCLEOTIDES

The approval of the first treatment for spinal muscular atrophy by 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. 

GENE THERAPY

Gene therapy is a new class of medicines that targets the root causes of genetic diseases. Biogen is committed to developing gene therapy as a fourth modality for a suite of disease indications, including CNS and ophthalmology. 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. Gene therapy expands our potential to treat previously intractable diseases by capitalizing on recent advances in our understanding of human genetics.