OUR PURPOSE PIONEERING SCIENCE PATIENTS OUR PEOPLE ENVIRONMENT COMMUNITY REPORTING 24 ENHANCING OUR STRATEGIC PORTFOLIO BIOGEN 2021 YEAR IN REVIEW Parkinson’s disease and movement disorders Parkinson’s disease, the second-most common neurodegenerative illness, is a progressive disorder of the central nervous system that causes nerve cell damage associated with tremors, stiffness and difficulty with balance and coordination. Biogen remains committed to advancing treatments for movement disorders. Although we had to discontinue BIIB054 (cinpanemab) following unsuccessful Phase 2 results, we are continuing to pursue promising science. – We are working with Denali Therapeutics, Inc. (Denali) to co-develop and co-commercialize BIIB122 (DNL151), a small molecule inhibitor of leucine-rich repeat kinase (LRRK2) for Parkinson’s disease. In 2021, positive results presented in Phase 1 and Phase 1b studies of the small molecule LRRK2 inhibitor, with safety and biomarker goals met in both studies. We’re now working to advance BIIB122 into late-stage clinical development. – Essential tremor (ET), one of the most common movement disorders, affects an estimated 6.4 million people in the U.S. alone. For people with ET, uncontrollable shaking of the hands, head, voice or legs can create difficulty eating, dressing, writing and pursuing other day-to-day activities. The Phase 2 KINETIC Study of SAGE-324 for the treatment of ET, conducted by our collaboration partner Sage Therapeutics, Inc., met its primary endpoint in 2021. At day 29, SAGE-324 demonstrated a 36% reduction in upper limb tremor amplitude from baseline in the total studied population. In a more severe population, SAGE-324 demonstrated a 41% reduction in upper limb tremor amplitude compared to baseline. Þ READ MORE ABOUT PHASE 2 KINETIC STUDY RESULTS Stroke Stroke is the fifth-leading cause of death in the U.S. and for those who survive, can involve a high risk of potentially severe disability 1 . Biogen is working to meet the significant need for improved treatments. – Acute Ischemic Stroke (AIS) 2 : 85% of strokes are AIS, which affects one in six people in their lifetime. In 2021, we acquired BIIB131 (TMS-007), an investigational drug for AIS, based on positive data from a Phase 2a study. AIS is caused by a blockage of blood supply to the brain, and current thrombolytics are limited in use due in part to increased risks of bleeding. The BIIB131 study met its primary safety objective with no incidence of bleeding and demonstrated positive impacts on both blood vessel reopening in the brain and patient functional recovery. It has been almost 25 years since the last thrombolytic agent was approved for AIS, and we believe this novel investigational drug may expand the number of eligible patients who could potentially receive thrombolytic therapy and thus have a higher chance of functional independence after stroke. We are evaluating the next steps for the clinical development of TMS-007, including plans for global studies. – Large hemispheric infarction (LHI): Representing 15% of stroke cases, LHI has a 40–80% mortality rate with high risk of severe disability. Currently, there are no approved therapies specific to LHI or that can prevent the edema and ensuing disability associated with LHI. Following our first-ever import of a clinical investigational drug into China in 2020, we reached another major milestone in 2021: enrolling the first patient in a pivotal Phase 3 study (CHARM) in China. CHARM is designed to evaluate BIIB093 (intravenous glibenclamide) for the prevention and treatment of severe cerebral edema resulting from LHI. The study plans to enroll 54 patients at 24 study sites in China, plus an additional 768 patients outside of China. BIIB093 also is being investigated in a Phase 2 study in patients with brain contusion following traumatic brain injury. Chronic Painful Neuropathy 3 One study with promising results in 2021 was the Phase 2 CONVEY study of vixotrigine (BIIB074), a non-opioid investigational oral pain drug being evaluated for the treatment of small fiber neuropathy (SFN), a condition often characterized by severe pain. Increasing the vixotrigine trial dose met statistical significance in the Patient Global Impression of Change (PGIC) at week 12, an important self-reported measure of a patient’s overall improvement since the start of the study. The totality of data from the program will inform potential doses for study in future Phase 3 clinical trials. Þ READ MORE ABOUT VIXOTRIGINE STUDY RESULTS 1. The World Health Organization. (2020, December 9). The top 10 causes of death . 2. Merkler, A., Parikh, N., & Mir, S. (2020, July 2). Risk of ischemic stroke in patients with coronavirus disease 2019 (COVID-19) vs patients with influenza . 3. Kamerman, P., Wadley, A., Davis, K., Hietaharju, A., Jain, P., Kopf, A., Meyer, A., Raja, S., Rice, A., Smith, B., Treede, R., & Wiffen, P. (2015, May). World Health Organization (WHO) essential medicines lists: where are the drugs to treat neuropathic pain?