OUR PURPOSE PIONEERING SCIENCE PATIENTS OUR PEOPLE ENVIRONMENT COMMUNITY REPORTING 30 ENHANCING OUR STRATEGIC PORTFOLIO BIOGEN 2021 YEAR IN REVIEW Gene therapy Decades of research have unveiled the genetic causes of many conditions, unlocking the potential of gene therapy: a drug administered once that can modify the disease-associated genetic information in a patient’s cells. Gene therapies have the potential to one day dramatically change healthcare, moving from disease management to potentially preventing, halting or curing a disease with one injection. Gene therapy is a significant part of Biogen’s focus in neurological and ophthalmological diseases, and we are investing in infrastructure, developing new partnerships and advancing RNA splicing technology. Gene therapy and ophthalmology – XLRP: A rare, inherited eye disease, X-linked retinitis pigmentosa (XLRP) typically begins with difficulty seeing at night, followed by restriction of the field of vision and eventually blindness, in most people by the age of 40. Patients living with XLRP currently have no approved treatments. Biogen is investigating one-time therapy for patients with XLRP: cotoretigene toliparvovec (BIIB112). Topline results from the Phase 2/3 XIRIUS study show that it did not meet its primary endpoint of demonstrating a statistically significant improvement. Positive trends were observed across several clinically relevant prespecified secondary endpoints, such as a measure of visual acuity under low light conditions. Þ READ MORE ABOUT THE XIRUS STUDY – Choroideremia: In ophthalmology, we’re also evaluating the safety and efficacy of timrepigene emparvovec (BIIB111/AAV2-REP1), a gene therapy being investigated for the one-time treatment of choroideremia, another rare inherited retinal disease 1 . While our Phase 3 STAR study did not meet its primary endpoint or key secondary endpoints, the clinical insights from this study may prove valuable in the future. – Other inherited diseases: In 2021, we entered an agreement with German-based ViGeneron GmbH to develop and commercialize gene therapy products based on adeno-associated virus (AAV) vectors to treat inherited eye diseases. We also formed a collaboration with Ginkgo Bioworks to develop a next-generation AAV production SPOTLIGHT Championing our local biotech community Biogen’s commitment to championing innovation extends beyond our walls. We support our local biotech community in a variety of ways, including as a sponsor of LabCentral, a first-of-its-kind shared laboratory space designed as a launchpad for high-potential life sciences and biotech startups. Each year, Biogen awards two “Golden Tickets” to innovative startup companies, which includes mentoring and one year of lab space for one scientist at LabCentral. This year’s selection process included a virtual competition where four finalists presented their proposed research to the R&D organization and an internal Biogen judging panel, which selected these winners: – Bolden Therapeutics, which is developing therapeutics that target a novel signaling pathway to promote adult hippocampal neurogenesis to treat CNS diseases. – Accure Health, which focuses on developing integrated solutions that rapidly digitize liquid biomarkers into quantitative, actionable information to improve early detection and precision treatment of cancer, neurodegeneration, and other complex diseases. platform. Recombinant AAV-based vectors are widely used to develop innovative gene therapies with the potential to treat certain neurological and neuromuscular diseases, yet manufacturing them is time-consuming and expensive. We see the potential to accelerate gene therapy development by applying Ginkgo Bioworks’ mammalian cell programming platform to improve the efficiency of AAV-producing plasmid vectors and cell lines. Þ READ MORE ABOUT OUR COLLABORATION WITH GINKGO BIOWORKS 1. Hanany, M., Rivolta, C., & Sharon, D. (2020, January 21). Worldwide carrier frequency and genetic prevalence of autosomal recessive inherited retinal diseases . Pictured, from left: Johnny Page, Co-founder & CEO of Bolden Therapeutics, and Jessica Sang, CEO & Co-founder of Accure.