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Item 1. Business

2022-02-03 compared with 2021-02-03 · 392 added, 283 removed, 765 unchanged (47% of the section changed)

Biogen is a global biopharmaceutical company focused on discovering, developing and delivering worldwide innovative therapies for people living with serious neurological and neurodegenerative diseases as well as related therapeutic adjacencies.

Our core growth areas include multiple sclerosis (MS) and neuroimmunology;

Alzheimer’s disease and dementia;

neuromuscular disorders, including spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS);

movement disorders, including Parkinson's disease;

ophthalmology;

and neuropsychiatry.

We are also focused on discovering, developing and delivering worldwide innovative therapies in our emerging growth areas of immunology;

acute neurology;

and neuropathic pain.

In addition, we commercialize biosimilars of advanced biologics.

We have a leading portfolio of medicines to treat multiple sclerosis (MS), have introduced the first approved treatment for spinal muscular atrophy (SMA) and are providing the first and only approved treatment to address a defining pathology of Alzheimer’s disease.

We also commercialize biosimilars of advanced biologics and focus on advancing our pipeline in neuroscience and specialized immunology.

Lastly, we are focused on accelerating our efforts in digital health to support our commercial and pipeline programs while also creating opportunities for potential digital therapeutics.

We support our drug discovery and development efforts through the commitment of significant resources to discovery, research and development programs and business development opportunities.

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SPINRAZA for the treatment of SMA;

ADUHELM for the treatment of Alzheimer's disease;

and FUMADERM for the treatment of severe plaque psoriasis.

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OCREVUS for the treatment of primary progressive MS (PPMS) and relapsing MS (RMS);

and other potential anti-CD20 therapies pursuant to our collaboration arrangements with Genentech, Inc.

and other potential anti-CD20 therapies, including mosunetuzumab, pursuant to our collaboration arrangements with Genentech, Inc.

(Genentech), a wholly-owned member of the Roche Group.

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We introduced the first approved treatment for SMA and are continuing to pursue research and development for potential advancements in the treatment of SMA.

We are also applying our scientific expertise to solve some of the most challenging and complex diseases, including Alzheimer's disease, ALS, Parkinson's disease, choroideremia (CHM), major depressive disorder, postpartum depression, X-linked retinitis pigmentosa (XLRP), systemic lupus erythematosus (SLE), cutaneous lupus erythematosus (CLE), cognitive impairment associated with schizophrenia (CIAS), stroke and neuropathic pain.

We are also applying our scientific expertise to solve some of the most challenging and complex diseases, including Alzheimer's disease, ALS, Parkinson's disease, major depressive disorder (MDD), postpartum depression (PPD), systemic lupus erythematosus (SLE), cutaneous lupus erythematosus (CLE), cognitive impairment associated with schizophrenia (CIAS), stroke and neuropathic pain.

Our innovative drug development and commercialization activities are complemented by our biosimilar business that expands access to medicines and reduces the cost burden for healthcare systems.

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(Samsung Bioepis), our joint venture with Samsung BioLogics Co., Ltd.

(Samsung BioLogics), we market and sell BENEPALI, an etanercept biosimilar referencing ENBREL, IMRALDI, an adalimumab biosimilar referencing HUMIRA, and FLIXABI, an infliximab biosimilar referencing REMICADE, in certain countries in Europe and have an option to acquire exclusive rights to commercialize these products in China.

Additionally, we have exclusive rights to commercialize two potential ophthalmology biosimilar products, SB11, a proposed ranibizumab biosimilar referencing LUCENTIS, and SB15, a proposed aflibercept biosimilar referencing EYLEA, in major markets worldwide, including the U.S., Canada, Europe, Japan and Australia.

We have also secured the exclusive rights to commercialize BYOOVIZ, a ranibizumab biosimilar referencing LUCENTIS, which was approved in the U.S., the European Union (E.U.) and the U.K.

during the third quarter of 2021.

For additional information on our collaboration arrangements with Samsung Bioepis, please read Note 18, Collaborative and Other Relationships , to our consolidated financial statements included in this report.

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Acquisitions, Collaborative and Other Relationships

BIIB118 Acquisition

In March 2020 we acquired BIIB118 (CK1 inhibitor), a novel CNS-penetrant small molecule inhibitor of casein kinase 1, for the potential treatment of patients with behavioral and neurological symptoms across various psychiatric and neurological diseases from Pfizer Inc.

We are developing BIIB118 for the potential treatment of irregular sleep wake rhythm disorder (ISWRD) in Parkinson’s disease and plan to develop BIIB118 for the potential treatment of sundowning in Alzheimer's disease.

Sangamo Therapeutics, Inc.

In April 2020 we closed a collaboration and license agreement with Sangamo Therapeutics, Inc.

(Sangamo) to develop and commercialize ST-501 for tauopathies, including Alzheimer’s disease;

ST-502 for synucleinopathies, including, Parkinson’s disease;

a third neuromuscular disease target;

and up to nine additional neurological disease targets to be identified and selected within a five-year period.

The companies are leveraging Sangamo's proprietary zinc finger protein technology delivered via adeno-associated virus to modulate the expression of key genes involved in neurological diseases.

In connection with the closing of this transaction, we purchased $225.0 million of Sangamo common stock, or approximately 24 million shares at approximately $9.21 per share.

Denali Therapeutics Inc.

In October 2020 we closed a collaboration and license agreement with Denali Therapeutics Inc.

(Denali) to co-develop and co-commercialize Denali’s small molecule inhibitors of leucine-rich repeat kinase 2 (LRRK2) for Parkinson’s disease.

In addition to the LRRK2 program, we also have an exclusive option to license two preclinical programs from Denali’s Transport Vehicle platform, including its Antibody Transport Vehicle (ATV):

ATV enabled anti-amyloid beta (Abeta) program and a second program utilizing its Transport Vehicle technology.

Further, we have a right of first negotiation on two additional Transport Vehicle-enabled therapeutics, should Denali decide to seek a collaboration for such programs.

As part of this collaboration we purchased approximately $465.0 million of Denali common stock in September 2020, or approximately 13 million shares at approximately $34.94 per share.

Sage Therapeutics, Inc.

In December 2020 we closed a global collaboration and license agreement with Sage Therapeutics, Inc.

(Sage) to jointly develop and commercialize zuranolone (SAGE-217) for the potential treatment of major depressive disorder, postpartum depression and other psychiatric disorders and SAGE-324 for the potential treatment of essential tremor and other neurological disorders.

In connection with the closing of this transaction we purchased $650.0 million of Sage common stock, or approximately 6.2 million shares at approximately $104.14 per share.

Bio-Thera Solutions

In April 2021 we entered into a commercialization and license agreement to develop, manufacture and commercialize BAT1806, a Phase 3 clinical stage anti-interleukin-6 (IL-6) receptor monoclonal antibody that is a proposed biosimilar referencing ACTEMRA.

In connection with this agreement, we made an upfront payment of $30.0 million to Bio-Thera Solutions.

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InnoCare Pharma Limited

In August 2021 we closed a collaboration and license agreement with InnoCare Pharma Limited (InnoCare) for orelabrutinib, an oral small molecule Bruton's tyrosine kinase inhibitor for the potential treatment of MS.

Orelabrutinib is currently being studied in a multi-country, placebo-controlled Phase 2 trial in relapsing-remitting MS (RRMS).

Under the terms of this collaboration, we have exclusive rights to orelabrutinib in the field of MS worldwide and certain autoimmune diseases outside of China (including Hong Kong, Macau and Taiwan), while InnoCare retains exclusive worldwide rights to orelabrutinib in the field of oncology and certain autoimmune diseases in China (including Hong Kong, Macau and Taiwan).

In connection with this agreement, we made an upfront payment of $125.0 million to InnoCare.

Mosunetuzumab

In January 2022 we exercised our option with Genentech to participate in the joint development and commercialization of mosunetuzumab, a late-stage bispecific antibody in development for B-cell non-Hodgkin’s lymphoma and other therapeutic areas.

In connection with this exercise, we recorded a $30.0 million option exercise fee payable to Genentech in December 2021.

BIIB115 Option Exercise

In December 2021 we exercised our option with Ionis and obtained a worldwide, exclusive, royalty-bearing license to develop and commercialize BIIB115, a preclinical investigational ASO in development for SMA.

In connection with this option exercise, we made an opt-in payment of $60.0 million to Ionis.

Samsung Bioepis - Biogen's Joint Venture with Samsung BioLogics

In January 2022 we entered into an agreement to sell to Samsung Biologics our equity in Samsung Bioepis.

Under the terms of the proposed transaction, we would receive $1.0 billion in cash at closing and $1.3 billion to be deferred over two payments of $812.5 million due at the first anniversary and $437.5 million due at the second anniversary of the closing of the transaction.

We would also be eligible to receive up to an additional $50.0 million upon the achievement of certain commercial milestones.

Closing of the transaction is currently anticipated in mid-2022, contingent on the effectiveness of a securities registration statement filed by Samsung Biologics and satisfaction of certain regulatory and other customary closing conditions.

For additional information on the proposed transaction and our collaboration arrangements with Samsung Bioepis, please read Note 18, Collaborative and Other Relationships, to our consolidated financial statements included in this report.

Other Key Developments

Aducanumab (Aβ mAb)

In July 2020 we completed the submission of a Biologics License Application (BLA) to the U.S.

Food and Drug Administration (FDA) for the approval of aducanumab, an anti-amyloid beta antibody candidate for the potential treatment of Alzheimer's disease that we are developing in collaboration with Eisai Co., Ltd.

In August 2020 the FDA accepted the BLA and granted Priority Review with a Prescription Drug User Fee Act (PDUFA) action date on March 7, 2021.

In November 2020 the FDA held a virtual meeting of the Peripheral and Central Nervous System Drugs Advisory Committee (the Advisory Committee) to review data supporting the BLA for aducanumab and to vote on questions presented at the meeting.

A majority of the Advisory Committee members voted against each of the questions presented at the meeting.

In January 2021 the FDA extended the review period for the BLA for aducanumab by three months.

The updated PDUFA action date is June 7, 2021.

As part of the ongoing review, we submitted a response to an information request by the FDA, including additional analyses and clinical data, which the FDA considered a Major Amendment to the application that will require additional time for review.

In October 2020 the European Medicines Agency (EMA) accepted for review the Marketing Authorization Application (MAA) for aducanumab.

In December 2020 the Ministry of Health, Labor and Welfare accepted for review the Japanese New Drug Application for aducanumab.

SB11 (referencing LUCENTIS)

In October 2020 the EMA accepted for review the MAA for SB11 and in November 2020 the FDA accepted the BLA for SB11.

We have exclusive rights to commercialize SB11 in major markets worldwide, including the U.S., Canada, Europe, Japan and Australia, pursuant to our 2019 agreement with Samsung Bioepis.

2020 Share Repurchase Programs

In October 2020 our Board of Directors authorized a program to repurchase up to $5.0 billion of our common stock (2020 Share Repurchase Program).

Our 2020 Share Repurchase Program does not have an expiration date.

All share repurchases under our 2020 Share Repurchase Program will be retired.

Healthy Climate, Healthy Lives

In September 2020 we announced Healthy Climate, Healthy Lives, a $250.0 million, 20-year initiative to eliminate our fossil fuels across our operations and collaborate with renowned institutions with the aim to improve health, especially for the world's most vulnerable populations.

ADUHELM (aducanumab)

In June 2021 the U.S.

Food and Drug Administration (FDA) granted accelerated approval of ADUHELM, which we are developing and commercializing in collaboration with Eisai Co., Ltd.

(Eisai), based on reduction in amyloid beta plaques observed in patients treated with ADUHELM.

As part of the accelerated approval, we will conduct a confirmatory trial to verify the clinical benefit of ADUHELM in patients with Alzheimer’s disease.

The FDA may withdraw approval if, among other things, the confirmatory trial fails to verify clinical benefit of ADUHELM, ADUHELM's benefit-risk is no longer positive or we fail to comply with the conditions of the accelerated approval.

In December 2021 the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a negative opinion on the Marketing Authorization Application (MAA) for aducanumab in Europe.

We are seeking a re-examination of the opinion by the CHMP.

In January 2022 the Centers for Medicare and Medicaid Services (CMS) released a proposed National Coverage Determination (NCD) decision memorandum stating the proposed NCD would cover FDA approved monoclonal antibodies that target amyloid for the treatment of Alzheimer's disease for people with Medicare only if they are enrolled in qualifying clinical trials.

We expect a final Medicare NCD by the second quarter of 2022, which should clarify Medicare reimbursement for the class of antibodies directed against amyloid.

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BIIB125 (zuranolone)

In June 2021 we and Sage Therapeutics, Inc.

(Sage) announced positive Phase 3 results for BIIB125 (zuranolone) for the potential treatment of MDD and PPD.

In October 2021 we and Sage announced our plan to submit a New Drug Application (NDA) to the FDA for zuranolone in the second half of 2022, with rolling submission expected to start in the first half of 2022.

The planned initial submission package will seek approval of zuranolone for MDD and an additional filing for PPD is anticipated in the first half of 2023.

Lecanemab (BAN2401)

In June 2021 the FDA granted Breakthrough Therapy designation for lecanemab, an anti-amyloid antibody for the potential treatment of Alzheimer's disease, which we are developing in collaboration with Eisai.

In September 2021 Eisai initiated a rolling submission to the FDA of a Biologics License Application (BLA) for lecanemab.

The BLA is being submitted under the accelerated approval pathway and is primarily based in clinical, biomarker and safety data from the Phase 2b clinical trial in patients with early Alzheimer's disease and confirmed amyloid pathology.

BYOOVIZ (ranibizumab-nuna)

In September 2021 we announced that the FDA has approved BYOOVIZ (ranibizumab-nuna), a biosimilar referencing LUCENTIS for the treatment of neovascular (wet) age-related macular degeneration, macular edema following retinal vein occlusion and myopic choroidal neovascularization.

In addition to the U.S.

approval, BYOOVIZ was approved in the E.U.

during the third quarter of 2021.

BIIB067 (tofersen)

In October 2021 we announced topline results from our pivotal Phase 3 VALOR study of BIIB067 (tofersen), an investigational antisense drug being evaluated for people with superoxide dismutase 1 (SOD1) amyotrophic lateral sclerosis (ALS), indicating that the primary endpoint was not met.

Exchange Offer

In February 2021 we completed a private offer to exchange (Exchange Offer) our tendered 5.200% Senior Notes due September 15, 2045 (2045 Senior Notes) for a new series of 3.250% Senior Notes due February 15, 2051 (2051 Senior Notes) and cash, and an offer to purchase our tendered 2045 Senior Notes for cash.

North Carolina Gene Therapy Manufacturing Facility

In March 2021 we announced our plans to build a new gene therapy manufacturing facility in RTP, North Carolina to support our gene therapy pipeline across multiple therapeutic areas.

The new facility will be approximately 175,000 square feet and is expected to be operational by the end of 2023.

Construction for this new facility began during the fourth quarter of 2021.

Solothurn, Switzerland Manufacturing Facility

In May 2021 we announced that a portion of our Solothurn manufacturing facility received a Good Manufacturing Practice (GMP) multi-product license from the Swiss Agency for Therapeutic Products (SWISSMEDIC).

Management Changes

In July 2020 we announced the appointment of Michael R.

McDonnell as Executive Vice President and Chief Financial Officer.

In July 2021 we announced the appointment of Rachid Izzar to the Executive Committee of the Company as well as Head of the Alzheimer's Disease and Dementia Business Unit.

In November 2021 we announced the retirement of Alfred Sandrock and the appointment of Priya Singhal, Head of Global Safety and Regulatory Sciences, as interim Head of Research and Development.

For additional information on our executive officers, please read the subsection entitled "Information about our Executive Officers" included in this report.

Product and Pipeline Developments

Core Growth Areas

Multiple Sclerosis and Neuroimmunology

TYSABRI (natalizumab)

• In March 2020 we made a regulatory submission to the EMA for a subcutaneous (SC) formulation of TYSABRI (natalizumab).

In June 2020 we submitted a Supplemental Biologics License Application for a SC formulation of natalizumab to the FDA.

The filings are supported by data from the DELIVER and REFINE studies, which demonstrated that natalizumab 300 mg SC every 4 weeks (Q4W) was comparable to standard 300 mg intravenous Q4W dosing with respect to clinical and magnetic resonance imaging (MRI) efficacy, pharmacokinetics/pharmacodynamics, immunogenicity and safety.

• In May 2020, through the 2020 American Academy of Neurology (AAN) Science Highlights virtual platform, an analysis of TYSABRI contributed to data demonstrating the reduced risk of progressive multifocal leukoencephalopathy (PML) through extended interval dosing (approximately every six weeks) as compared to the currently approved Q4W dosing.

• In September 2020, at MSVirtual2020, the eighth joint meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis and the European Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS-ECTRIMS), we presented new real-world MRI data suggesting that the effectiveness of extended interval dosing of TYSABRI is similar to the approved Q4W dosing.

TECFIDERA (dimethyl fumerate)

• In April 2021 China's National Medical Products Administration approved TECFIDERA for the treatment of RMS.

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VUMERITY (diroximel fumarate;

• In May 2020, through the 2020 AAN Science Highlights virtual platform, we announced new data that support VUMERITY as an important oral treatment option in RMS.

• In September 2020, at MSVirtual2020, the eighth joint meeting of ACTRIMS-ECTRIMS, we presented new data further defining the effectiveness and safety profile of VUMERITY.

• In November 2020 we submitted a MAA for VUMERITY to the EMA.

• In November 2021 the European Commission (EC) granted marketing authorization for VUMERITY in the E.U.

for the treatment of RRMS.

PLEGRIDY (peginterferon beta-1a)

• In December 2020 the European Commission (EC) approved a new intramuscular (IM) injection route of administration for PLEGRIDY for the treatment of relapsing-remitting MS (RRMS).

• In January 2021 the FDA approved a new IM injection route of administration for PLEGRIDY for the treatment of RRMS.

• In January 2021 the FDA approved a new intramuscular (IM) injection route of administration for PLEGRIDY for the treatment of RRMS.

TYSABRI (natalizumab)

• In April 2021 the EC granted marketing authorization for a new subcutaneous (SC) injection route of administration for TYSABRI for the treatment of RRMS.

• In April 2021, at the 2021 American Academy of Neurology (AAN) Virtual Annual Meeting, we presented new data on quality of life benefits and analyses of extended interval dosing with TYSABRI.

• In August 2021 we announced results from the two-year prospective, randomized, interventional, controlled, open-label Phase 3b NOVA study.

NOVA was designed to estimate a potential difference between the efficacy of every six-weeks (Q6W) 300mg intravenous (IV) dosing compared to the efficacy of the approved every four-week (Q4W) dose in people treated with TYSABRI for RRMS.

Alzheimer's Disease and Dementia

Aducanumab (Aβ mAb)

• In March 2020 the first patient was dosed in the aducanumab re-dosing study, EMBARK, which is a global re-dosing clinical study designed to evaluate aducanumab in eligible Alzheimer’s disease patients who were actively enrolled in aducanumab studies (PRIME, EVOLVE, EMERGE and ENGAGE) in March 2019.

• In November 2020 we presented on the study design of the ongoing EMBARK re-dosing study of aducanumab at the 2020 Clinical Trials on Alzheimer's Disease digital conference.

ADUHELM (aducanumab)

• In June 2021 the FDA granted accelerated approval for ADUHELM as the first and only Alzheimer's disease treatment to address a defining pathology of the disease by reducing amyloid beta plaques in the brain.

• In July 2021 the FDA approved an updated label for ADUHELM injection 100 mg/mL solution.

• In July 2021, at the Alzheimer's Association International Conference (AAIC), we presented the design for the first real-world observational Phase 4 study of Alzheimer's disease called ICARE AD-US.

• In November 2021, at the 2021 Clinical Trials on Alzheimer's Disease (CTAD) conference, we announced that data from the ADUHELM Phase 3 clinical trials showed a statistically significant correlation between plasma p-tau reduction and less cognitive and functional decline in Alzheimer’s disease.

We also presented data from the Phase 3b redosing study, EMBARK, which examined the impact of patients with Alzheimer's disease stopping ADUHELM treatment for an extended period of time before re-initiating treatment.

• In November 2021 we received a negative trend vote on the aducanumab MAA in the E.U.

• In December 2021 the CHMP adopted a negative opinion on the MAA for aducanumab.

• In December 2021 the First Committee on New Drugs (NDC) of the Pharmaceutical Affairs and Food Sanitation Council that advises the Ministry of Health, Labour and Welfare (MHLW) in Japan decided to continue deliberations on the application for the manufacturing and marketing approval of aducanumab for the treatment of Alzheimer's disease.

• In January 2022 the CMS released a proposed NCD decision memorandum, stating the proposed NCD would cover FDA approved monoclonal antibodies that target amyloid for the treatment of Alzheimer's disease for people with Medicare only if they are enrolled in qualifying clinical trials.

BAN2401 (lecanemab)

• In September 2020 the first patient was dosed in the Phase 3 AHEAD 3-45 clinical study of BAN2401, an anti-amyloid beta antibody, in individuals with preclinical Alzheimer’s disease who have intermediate or elevated levels of amyloid in their brains.

We are collaborating with Eisai on the development of BAN2401.

• In June 2021 the FDA granted Breakthrough Therapy designation for lecanemab for the potential treatment of Alzheimer's disease.

• In July 2021, at the AAIC, Eisai presented results of a longitudinal preliminary assessment of the clinical effects of lecanemab following 18 months of treatment in the open-label extension (OLE) of the Phase 2b proof-of-concept study in subjects with early Alzheimer's disease.

• In September 2021 Eisai initiated a rolling submission to the FDA of a BLA for lecanemab.

The BLA is being submitted under the accelerated approval pathway and is primarily based on clinical, biomarker and safety data from the Phase 2b clinical trial (Study 201) in patients with early Alzheimer's disease and confirmed amyloid pathology.

• In November 2021 Eisai presented results of new clinical, biomarker and safety assessments of brain amyloid reduction and five-year clinical status of people living with early Alzheimer's disease from the

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lecanemab Phase 2b 201 and the OLE studies.

The findings were presented and discussed in a late-breaking roundtable session at the 2021 CTAD conference.

• In December 2021 we and Eisai announced that lecanemab was granted Fast Track designation by the FDA.

Neuromuscular Disorders

SPINRAZA (nusinersen)

• In March 2020 the first patient was dosed in the global DEVOTE study, which is evaluating the safety, tolerability and potential for even greater efficacy of SPINRAZA when administered at a higher dose than currently approved for the treatment of SMA.

• In March 2020 a study on the efficacy and safety of SPINRAZA in teen and adult patients was published in Lancet Neurology , showing clinically meaningful improvements in motor function in a real-world cohort.

This study included 139 teens and adults with later-onset SMA (age 16-65 years) from 10 neuromuscular treatment centers in Germany.

Patients were followed for 6-14 months and experienced statistically significant increases in HFMSE (Hammersmith Functional Motor Scale Expanded) scores compared to baseline at 6 months, 10 months and 14 months.

Clinically meaningful improvements (≥3 points increase) in HFMSE scores were seen in 28% of patients at 6 months, 35% of patients at 10 months and 40% of patients at 14 months.

The most frequent adverse events were headache, back pain and nausea.

• In June 2020 we announced new results from NURTURE, the longest study of presymptomatic patients with SMA.

In infants genetically diagnosed with SMA, new data demonstrated that early and sustained treatment with SPINRAZA for up to 4.8 years enabled unprecedented survival.

Patients continued to maintain and make progressive gains in motor function compared to the natural course of the disease.

These results were presented at the virtual Cure SMA Research & Clinical Care Meeting.

• In May 2020, through the 2020 AAN Science Highlights virtual platform, we announced additional data from the SPINRAZA clinical development program that further demonstrated the sustained efficacy and longer-term safety of SPINRAZA in a broad range of patients with SMA.

The SHINE open-label extension study (NCT02594124) has enrolled 292 patients (infants through teenagers) from 5 previous SPINRAZA clinical studies, including ENDEAR.

New findings from the SHINE study show that treatment with SPINRAZA resulted in motor function improvement or disease stabilization in toddlers, children and young adults who were treated continuously, some for up to six and a half years.

BIIB067 (tofersen) - ALS

• In July 2020 positive results from a Phase 1/2 study of tofersen for the potential treatment of superoxide dismutase 1 (SOD1) ALS were published in The New England Journal of Medicine .

Final Phase 1/2 study results demonstrated proof-of-concept and proof-of-biology of tofersen.

BIIB105 (ataxin-2 ASO) - ALS

• In September 2020 the first patient in a Phase 1 study of BIIB105, an antisense oligonucleotide (ASO) targeting ataxin-2 in ALS, was dosed.

• In January 2021 the first patient was dosed in the global RESPOND study, which will examine the clinical benefit and assess the safety of SPINRAZA in infants and children with SMA.

• In April 2021, at the AAN 2021 Virtual Annual Meeting, we announced new data from the Phase 2/3 DEVOTE study.

Initial findings from the DEVOTE study suggest no new safety concerns and support continued development of a higher dose of SPINRAZA.

• In June 2021, at the virtual Cure SMA Research & Clinical Care Meeting, we announced new data on the long-term efficacy of SPINRAZA.

• In September 2021 we announced plans to initiate a global Phase 3b clinical study, ASCEND.

The ASCEND study is designed to evaluate the clinical outcomes and assess the safety of a higher dose of SPINRAZA in children, teens and adults with later-onset SMA following treatment of Evrysdi.

Movement Disorders

BIIB101 (ION464) - Multiple System Atrophy

• In July 2020 the first patient in the Phase 1 study of BIIB101, an ASO targeting alpha synuclein in multiple system atrophy, was dosed.

Emerging Growth Areas

Dapirolizumab Pegol (anti-CD40L) - SLE

• In August 2020 the first patient was dosed in the Phase 3 program for dapirolizumab pegol in patients with active SLE despite being treated by standard of care therapies.

Dapirolizumab pegol is being developed in collaboration with UCB Pharma S.A.

BIIB059 (anti-BDCA2) - CLE/SLE

• In June 2020 we shared positive data from the 16-week CLE portion of the Phase 2 LILAC study.

The study evaluated the efficacy and safety of BIIB059, a fully humanized IgG1 monoclonal antibody (mAb) targeting blood dendritic cell antigen 2 (BDCA2) expressed on plasmacytoid dendritic cells (pDCs).

The data were presented at the European E-Congress of Rheumatology (EULAR).

• In November 2020 we shared positive data from the 24-week SLE portion of the Phase 2 LILAC study (part A) demonstrating that BIIB059 was associated with a statistically significant reduction in total active joint count.

These data, along with the previously reported findings from the CLE portion of the LILAC study, were presented at the American College of Rheumatology’s virtual ACR Convergence 2020.

SAGE-324 (GABA A receptor PAM)

• In April 2021 we and Sage reported that the Phase 2 KINETIC study evaluating SAGE-324 in the treatment of patients with essential tremor (ET) met its primary endpoint.

Neuropsychiatry

BIIB125 (zuranolone)

• In June 2021 we and Sage announced positive results from the Phase 3 WATERFALL study for zuranolone, an investigational two-week, once-daily therapeutic being evaluated for MDD.

• In October 2021 we and Sage shared positive data from the LANDSCAPE and NEST clinical development program.

This study evaluated the efficacy and safety of zuranolone for the treatment of MDD and PPD.

The data was presented at the European College of Neuropsychopharmacology Congress.

• In October 2021 we and Sage announced plans to submit a NDA to the FDA for zuranolone for the potential treatment of MDD in the second half of 2022 with rolling submission expected to start in early 2022.

Plans also include the submission of a NDA to the FDA for zuranalone for the treatment of PPD, in the first half of 2023.

• In December 2021 we and Sage announced positive data from the 12-month Phase 3 open-label SHORELINE study for zuranolone.

The SHORELINE study, part of the LANDSCAPE clinical program, was designed to naturalistically follow adult patients with MDD and evaluate the safety and tolerability of zuranolone as well as the need for repeat dosing for up to one year.

Specialized Immunology

BIIB059 (anti-BDCA2) - SLE

• In June 2021 the first patient was dosed in the Phase 3 TOPAZ-1 study of BIIB059 for SLE.

The Phase 3 study will evaluate the clinical efficacy and assess the safety of BIIB059 in participants with active SLE.

Neuropathic Pain

BIIB074 (vixotrigine)

• In September 2021 we announced positive results that the Phase 2 CONVEY study of vixotrigine, a non-opioid investigational oral pain drug being evaluated for the treatment of small fiber neuropathy.

The CONVEY study 200 mg twice daily arm met its primary endpoint.

The CONVEY study 350 mg twice daily arm did not meet its primary endpoint.

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• In April 2021 we entered into a commercialization and license agreement to develop, manufacture and commercialize BAT1806, a Phase 3 clinical stage anti-interleukin-6 (IL-6) receptor monoclonal antibody that is a proposed biosimilar referencing ACTEMRA (tocilizumab).

• In June 2021 we and Bio-Thera Solutions, Ltd.

(Bio-Thera) announced positive results that the Phase 3 study of BAT1806, a proposed biosimilar referencing ACTEMRA (tocilizumab), met its primary endpoint.

Samsung Bioepis - Biogen's Joint Venture with Samsung BioLogics

• In May 2020 Samsung Bioepis announced that the primary endpoints were met in the randomized, double-masked, Phase 3 trial comparing the efficacy, safety and immunogenicity of SB11 to the reference product (LUCENTIS).

Ranibizumab is an anti-VEGF (vascular endothelial growth factor) for retinal vascular disorders, which are a leading cause of blindness.

• In June 2020 Samsung Bioepis initiated a Phase 3 study for SB15, a proposed aflibercept biosimilar referencing EYLEA.

EYLEA is widely used to treat ophthalmologic conditions such as neovascular (wet) age-related macular degeneration, macular edema following retinal vein occlusion, diabetic macular edema (DME) and diabetic retinopathy in patients with DME.

Discontinued Programs

• In March 2020 we announced that the Phase 2 OPUS study investigating natalizumab as an adjunctive therapy in adults with drug-resistant focal epilepsy did not meet its primary endpoint.

Safety data were in-line with the known safety profile of natalizumab.

Based on these results, we discontinued development of natalizumab in drug-resistant focal epilepsy.

• In October 2020 we announced that the Phase 2 AFFINITY study of opicinumab (anti-LINGO) in MS did not meet its primary or secondary endpoints.

Based on these results, we discontinued development of opicinumab.

• In February 2021 we announced that the Phase 2 SPARK study of BIIB054 (cinpanemab) in Parkinson's disease did not meet its primary or secondary endpoints.

Based on these results, we discontinued development of BIIB054.

• In June 2021 Samsung Bioepis announced that the CHMP adopted a positive opinion of BYOOVIZ (ranibizumab-nuna), a biosimilar referencing LUCENTIS, and in August 2021 BYOOVIZ was approved by the EMA.

• In September 2021 Samsung Bioepis announced the FDA approval of BYOOVIZ.

Digital Health

• In January 2021 we announced a virtual research study, in collaboration with Apple Inc., to investigate the role Apple Watch and iPhone could play in monitoring cognitive performance and screening for decline in cognitive health including mild cognitive impairment (MCI).

• In December 2021 we announced an expanded collaboration with TheraPanacea focused on multiple therapeutic areas in neuroscience.

The expanded collaboration aims to leverage machine learning and artificial intelligence analysis to develop digital health solutions that may improve patient care, accelerate drug development, and further the understanding of the underlying pathologies of neurological diseases.

Discontinued or Suspended Programs

• In May 2021 we announced that the Phase 2/3 XIRIUS study of cotoretigene toliparvovec (BIIB112), a gene therapy being investigated as a one-time therapy for patients with X-linked retinitis pigmentosa, did not meet its primary endpoint.

Based on these results, we suspended further development based on the decision of management as part of its strategic review process.

• In June 2021 we announced that the Phase 3 STAR study of timrepigene emparvovec (BIIB111), an investigational gene therapy for the potential treatment of choroideremia, did not meet its primary endpoint.

Based on these results, we suspended further development based on the decision of management as part of its strategic review process.

• In June 2021 we announced that the Phase 2 TANGO study of BIIB092 (gosuranemab), an investigational anti-tau antibody that was being evaluated as a potential treatment for Alzheimer's disease, did not meet its primary endpoint.

Based on these results, we discontinued development of gosuranemab.

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Marketed Products

The following graph shows our revenues by product and revenues from anti-CD20 therapeutic programs for the years ended December 31, 2020, 2019 and 2018.

The following graph shows our revenue by product and revenue from anti-CD20 therapeutic programs for the years ended December 31, 2021, 2020 and 2019.

(1) Fumarate includes TECFIDERA and VUMERITY.

VUMERITY became commercially available in the U.S.

in November 2019.

VUMERITY became commercially available in the E.U.

during the fourth quarter of 2021.

(2) Interferon includes AVONEX and PLEGRIDY.

(3) For 2020, 2019 and 2018 other includes FAMPYRA, FUMADERM, BENEPALI, IMRALDI and FLIXABI.

For 2020 and 2019 other also includes VUMERITY, which became commercially available in the U.S.

in November 2019.

For 2018 other also includes ZINBRYTA, which was voluntary withdrawn from the market in March 2018.

(3) In June 2021 the FDA granted accelerated approval of ADUHELM, which became commercially available in the U.S.

during the second quarter of 2021.

For additional information, please read Note 18, Collaborative and Other Relationships - Eisai Co., Ltd.

- ADUHELM Collaboration Agreement , to our consolidated financial statements included in this report.

(4) Other includes FAMPYRA, FUMADERM, BENEPALI, IMRALDI and FLIXABI.

(5) Anti-CD20 therapeutic programs include RITUXAN, RITUXAN HYCELA, GAZYVA and OCREVUS.

Product sales for TECFIDERA, AVONEX, TYSABRI and SPINRAZA each accounted for more than 10.0% of our total revenues for the years ended December 31, 2020, 2019 and 2018.

For additional financial information about our product and other revenues and geographic areas where we operate, please read Note 4, Revenues, and Note 24, Segment Information, to our consolidated financial statements included in this report and Item 6.

Selected Financial Data and Item 7.

Product sales for TECFIDERA, AVONEX, TYSABRI and SPINRAZA each accounted for more than 10.0% of our total revenue for the years ended December 31, 2021, 2020 and 2019.

For additional financial information about our product and other revenue and geographic areas where we operate, please read Note 4, Revenue, and Note 24, Segment Information, to our consolidated financial statements included in this report and Item 7.

Management's Discussion and Analysis of Financial Condition and Results of Operations included in this report.

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Risk Factors included in this report.

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Multiple Sclerosis and Neuroimmunology

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RMS in the U.S.

RRMS in the E.U.

Alkermes Pharma Ireland Limited, a subsidiary of Alkermes plc (Alkermes) U.S.

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(Acorda) France

For additional information on our collaboration arrangements with Alkermes and Acorda, please read Note 18, Collaborative and Other Relationships, to our consolidated financial statements included in this report.

Neuromuscular Disorders

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The severity of SMA correlates with the amount of SMN protein.

People with Type 1 SMA, the most severe life-threatening form, produce very little SMN protein and do not achieve the ability to sit without support, and typically do not live beyond two years of age without respiratory support and nutritional interventions.

People with Type 1 SMA, the most severe life-threatening form, produce very little SMN protein and do not

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achieve the ability to sit without support, and typically do not live beyond two years of age without respiratory support and nutritional interventions.

People with Type 2 and Type 3 SMA produce greater amounts of SMN protein and have less severe, but still life-altering, forms of SMA.

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For additional information on our collaboration arrangements with Ionis, please read Note 18, Collaborative and Other Relationships, to our consolidated financial statements included in this report.

Alzheimer's Disease

Alzheimer's disease is characterized by two abnormalities in the brain:

amyloid plaques and neurofibrillary tangles.

Amyloid plaques, which are found in the tissue between the nerve cells, are unusual clumps of a protein called beta amyloid along with degenerating bits of neurons and other cells.

Our Alzheimer's disease product and major market is as follows:

Product Indication Collaborator Major Market

Alzheimer's disease Eisai U.S.

For additional information on our collaboration arrangements with Eisai, please read Note 18, Collaborative and Other Relationships, to our consolidated financial statements included in this report.

Biosimilars are a group of biologic medicines that are similar to currently available biologic therapies developed by companies known as "originators".

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BENEPALI, an etanercept biosimilar referencing ENBREL, IMRALDI, an adalimumab biosimilar referencing HUMIRA, and FLIXABI, an infliximab biosimilar referencing REMICADE.

We also have an option to acquire exclusive rights to commercialize BENEPALI, IMRALDI and FLIXABI in China.

We have also secured the exclusive rights to commercialize BYOOVIZ, a ranibizumab biosimilar referencing LUCENTIS, which was approved in the U.S., the E.U.

during the third quarter of 2021.

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Our current biosimilar products and major markets are as follows:

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For additional information on our collaboration arrangements with Samsung Bioepis, please read Note 18, Collaborative and Other Relationships, to our consolidated financial statements included in this report.

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Genentech Relationships

We have agreements with Genentech that entitle us to certain business and financial rights with respect to RITUXAN, RITUXAN HYCELA, GAZYVA, OCREVUS and other potential anti-CD20 therapies.

We have agreements with Genentech that entitle us to certain business and financial rights with respect to RITUXAN, RITUXAN HYCELA, GAZYVA, OCREVUS and other potential anti-CD20 therapies, including mosunetuzumab.

Our current anti-CD20 therapeutic programs and major markets are as follows:

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In combination with chemotherapy followed by GAZYVA alone for previously untreated follicular lymphoma U.S.

For additional information on our collaboration arrangements with Genentech, please read Note 1, Summary of Significant Accounting Policies, and Note 18, Collaborative and Other Relationships, to our consolidated financial statements included in this report.

For additional information on our collaboration arrangements with Genentech, please read Note 18, Collaborative and Other Relationships, to our consolidated financial statements included in this report.

Product Indication Collaborator Major Markets

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Our patient representatives have access to a suite of financial assistance tools.

With those tools, we help patients understand their insurance coverage and, if needed, help patients compare and select new insurance options and programs.

With those tools, we help patients understand their

insurance coverage and, if needed, help patients compare and select new insurance options and programs.

In the U.S., we have established programs that provide co-pay assistance or free marketed product for qualified uninsured or underinsured patients, based on specific eligibility criteria.

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We have a value-based contracting program designed to align the price of our therapies to the value our therapies deliver to patients.

We also work with regulators, clinical

researchers, ethicists, physicians and patient advocacy organizations and communities, among others, to determine how best to address requests for access to our investigational therapies in a manner that is consistent with our patient-focused values and compliant with regulatory standards and protocols.

We also work with regulators, clinical researchers, ethicists, physicians and patient

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advocacy organizations and communities, among others, to determine how best to address requests for access to our investigational therapies in a manner that is consistent with our patient-focused values and compliant with regulatory standards and protocols.

In appropriate situations, patients may have access to investigational therapies through Early Access Programs, single patient access or emergency use based on humanitarian or compassionate grounds.

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We and Eisai co-promote AVONEX, TYSABRI and TECFIDERA in Japan in certain settings.

We and Eisai co-promote ADUHELM with a region-based profit split.

RITUXAN, RITUXAN HYCELA, GAZYVA and OCREVUS are marketed by the Roche Group and its sublicensees.

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We distribute BENEPALI, IMRALDI and FLIXABI in certain countries in Europe and have an option to acquire exclusive rights to distribute these products in China.

Our product sales to two wholesale distributors each accounted for more than 10.0% of our total revenues for the years ended December 31, 2020, 2019 and 2018, and on a combined basis, accounted for approximately 45.8%, 47.0% and 50.0% of our gross product revenues for the years ended December 31, 2020, 2019 and 2018, respectively.

For additional information, please read Note 4, Revenues , to our consolidated financial statements included in this report.

Our product sales to two wholesale distributors each accounted for more than 10.0% of our total revenue for the years ended December 31, 2021, 2020 and 2019, and on a combined basis, accounted for approximately 38.9%, 45.8% and 47.0% of our gross product revenue for the years ended December 31, 2021, 2020 and 2019, respectively.

For additional information, please read Note 4, Revenue , to our consolidated financial statements included in this report.

Patents and Other Proprietary Rights

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Regulatory exclusivity, which may consist of regulatory data protection and market protection, also can provide meaningful protection for our products.

Regulatory data protection provides to the holder of a drug or biologic marketing authorization, for a set period of time, the exclusive use of the proprietary pre-clinical and clinical data that it created at

significant cost and submitted to the applicable regulatory authority to obtain approval of its product.

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regulatory authority to obtain approval of its product.

After the period of exclusive use, third-parties are permitted to reference such data in abbreviated applications for approval and to market (subject to any applicable market protection) their generic drugs and biosimilars.

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and other territories covering various aspects of our products that may, if issued, extend exclusivity beyond the expiration of the patents listed in the table.

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Product Territory Patent No.

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Europe 1131065 Formulations of dialkyl fumarates and their use for treating autoimmune diseases 2024 (3)

Europe 2137537 Methods of use 2028 (4)

PLEGRIDY U.S.

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9,493,567 Methods of treatment 2027

10,233,245 Methods of treatment 2027

Europe 1485127 Methods of use 2023 (2)

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10,080,733 Crystalline forms, pharmaceutical compositions and methods of treatment 2033

Europe 2,970,101 Crystalline forms, pharmaceutical compositions and methods of treatment

Prodrugs of fumarates and their use in treating various diseases 2034

SPINRAZA U.S.

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Europe 3,449,926 Compositions and methods for modulation of SMN2 splicing 2030

8,906,367 Method of providing disease-specific binding molecules and targets 2032 (10)

10,131,708 Methods of treating Alzheimer's disease 2028

Footnotes follow on next page.

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(1) In addition to patent protection, certain of our products are entitled to regulatory exclusivity in the U.S.

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(3) This patent is subject to granted SPCs in certain European countries, which extended the patent term in those countries to 2024.

(4) This patent was revoked in a European opposition.

This decision is being appealed.

(4) This patent is subject to granted SPCs in certain European countries, which extended the patent term in those countries to 2024.

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(9) This patent is subject to granted SPCs in certain European countries, which extended the patent term in those countries to 2031.

(10) This patent is subject to granted SPCs in certain European countries, which extended the patent term in those countries to 2031.

(10) A patent with this subject matter may be entitled to patent term extension in the U.S.

The existence of patents does not guarantee our right to practice the patented technology or commercialize the patented product.

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Risk Factors included in this report, and the discussion of legal proceedings related to certain patents described above is set forth in Note 20, Litigation, to our consolidated financial statements included in this report.

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Competition in the biopharmaceutical industry is intense.

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The development of new or improved treatment options or standards of care or cures for the diseases our products treat reduces and could eliminate the use of our products or may limit the utility and application of ongoing clinical trials for our product candidates.

In addition, the commercialization of certain of our own approved products, products of our collaborators and pipeline product candidates may

negatively impact future sales of our existing products.

In addition, the commercialization of certain of our own approved products, products of our collaborators and pipeline product candidates may negatively impact future sales of our existing products.

We also face increased competitive pressures from the introduction of generic versions, prodrugs and biosimilars of existing products and products approved under abbreviated regulatory pathways.

Such products are likely to be sold at substantially lower prices than branded products, which may significantly reduce both the price that we are able to charge for our products and the volume of products we sell.

In addition, in some markets, when a generic or biosimilar version of one of our products is commercialized, it may be automatically substituted for our product and significantly reduce our revenues in a short period of time.

We believe our long-term competitive position depends upon our success in discovering and developing innovative, cost-effective products that serve unmet medical needs, along with our ability to manufacture products efficiently and to launch and market them effectively in a highly competitive environment.

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Multiple Sclerosis

TECFIDERA, AVONEX, PLEGRIDY, TYSABRI and VUMERITY each compete with one or more of the following products as well as generic and biosimilar versions of such products:

TECFIDERA, AVONEX, PLEGRIDY, TYSABRI and VUMERITY each compete with one or more of the following branded products as well as generic and biosimilar versions of these products:

Competing Product Competitor

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OCREVUS (ocrelizumab) Genentech

PONVORY (ponesimod) Janssen Pharmaceutical Companies of Johnson & Johnson

(interferon-beta-1) EMD Serono

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KESIMPTA (ofatumumab) Novartis AG

In addition, multiple TECFIDERA generic entrants are now in the U.S.

Multiple TECFIDERA generic entrants are now in the U.S.

market and have deeply discounted prices compared to TECFIDERA.

The generic competition for TECFIDERA significantly reduced our TECFIDERA revenues during the year ended December 31, 2020, and is expected to have a

substantial negative impact on our TECFIDERA revenues for as long as there is generic competition.

The generic competition for TECFIDERA has significantly reduced our TECFIDERA revenue and is expected to continue to have a substantial and increasing negative impact on our U.S.

TECFIDERA revenue in the future.

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In May 2021 the European General Court annulled the EMA's decision not to validate applications for approval of TECFIDERA generics on the basis that the EMA conducted the wrong assessment when determining TECFIDERA's entitlement to regulatory data and marketing protection.

Our Company, the EMA and the EC have each appealed the General Court’s decision as wrongly decided and the appeal is pending.

In November 2021 the CHMP of the EMA issued an ad hoc opinion referencing the General Court’s decision which concluded that "the totality of the available data cannot establish that [monoethyl fumarate] exerts a clinically relevant therapeutic contribution within FUMADERM." The EC will decide TECFIDERA’s entitlement to regulatory data and market protection.

If data and market protection is not upheld, we could face generic competition in the E.U.

as early as the first half of 2022, which would have an adverse impact on our TECFIDERA sales in the E.U.

and our results of operations.

FAMPYRA is indicated as a treatment to improve walking in adult patients with MS who have a walking disability and is the first treatment that addresses this unmet medical need with demonstrated efficacy in people with all types of MS.

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Spinal Muscular Atrophy

We face competition from a gene therapy product that was approved in the U.S.

and a new oral product that was approved in the U.S.

and has been accepted for review in the E.U.

We expect that we will experience competition from both products in additional jurisdictions in the future.

We face competition from a gene therapy product and an oral product.

We expect that we will experience competition from both products in additional jurisdictions in the future, which may adversely affect our sales of SPINRAZA.

Additionally, we are aware of other products now in development that, if launched, may also compete with SPINRAZA.

Future sales of SPINRAZA may be adversely affected by the commercialization of competing products.

FUMADERM competes with several different types of therapies in the psoriasis market within Germany, including oral systemics such as methotrexate and cyclosporine.

FUMADERM competes with several different types of therapies in the psoriasis market within

Germany, including oral systemics such as methotrexate and cyclosporine.

BENEPALI, IMRALDI and FLIXABI, the three biosimilar products we currently commercialize in certain countries in Europe for Samsung Bioepis, compete with their reference products, ENBREL, HUMIRA and REMICADE, respectively, as well as other biosimilars of those reference products.

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Our research efforts are focused on better understanding the underlying biology of diseases so we can discover and deliver treatments that have the potential to make a real difference in the lives of patients with high unmet medical needs.

By applying our expertise in biologics and our growing capabilities in small molecule, antisense, gene therapy, gene editing and other technologies, we target specific medical needs where we believe new or better treatments are needed.

By applying our expertise in biologics and our growing capabilities in small molecule, antisense, gene therapy, gene editing and other technologies, we target specific

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medical needs where we believe new or better treatments are needed.

We intend to continue committing significant resources to targeted research and development opportunities where there is a significant unmet need and where a drug candidate has the potential to be highly differentiated.

As part of our ongoing research and development efforts, we have devoted significant resources to conducting clinical studies to advance the development of new pharmaceutical products and technologies and to explore the utility of our existing products in treating disorders beyond those currently approved in their labels.

As part of our ongoing research and development efforts, we have devoted significant resources to conducting clinical studies to advance the development of new pharmaceutical products and

technologies and to explore the utility of our existing products in treating disorders beyond those currently approved in their labels.

For additional information on our research and development expense included in our consolidated statements of income, please read Item 7.

Management's Discussion and Analysis of Financial Condition and Results of Operations included in this report.

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The table below highlights our current research and development programs that are in clinical trials and the current phase of such programs.

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Risk Factors included in this report.

Core Growth Areas MS and Neuroimmunology BIIB061 (oral remyelination) - MS Phase 1

MS and Neuroimmunology BIIB135 (orelabrutinib)* Phase 2

BIIB061 (oral remyelination) - MS Phase 1

BIIB091 (BTK inhibitor) - MS Phase 1

BIIB107 (anti-VLA4) - MS Phase 1

Alzheimer's Disease and Dementia Aducanumab (Aβ mAb) * - Alzheimer's

Filed in U.S., E.U.

BAN2401 (lecanemab) * - Alzheimer's

BIIB092 (gosuranemab) - Alzheimer's Phase 2

BIIB076 (anti-tau mAb) - Alzheimer's Phase 1

Alzheimer's Disease and Dementia Aducanumab (Aβ mAb)* - Alzheimer's Filed in E.U., Japan, Other Markets

Lecanemab (Aβ mAb)* - Alzheimer's Phase 3

BIIB080 tau ASO) - Alzheimer's Phase 1

BIIB076 (anti-tau mAb) - Alzheimer's Phase 1

Neuromuscular Disorders,

including SMA and ALS BIIB067 (tofersen) - ALS Phase 3

including SMA and ALS Tofersen (SOD1 ASO) - ALS Phase 3

BIIB078 (IONIS-C9 Rx ) # - ALS

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BIIB100 (XP01 inhibitor) - ALS Phase 1

BIIB110 (ActRIIA/B ligand trap) - SMA Phase 1

Parkinson's Disease and

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BIIB122 (DNL151) * - Parkinson's

Ophthalmology BIIB111 (timrepigene emparvovec) - CHM Phase 3

BIIB112 (RPGR gene therapy) - XLRP Phase 2/3

Neuropsychiatry BIIB125 (zuranolone)* - PPD Phase 3

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BIIB104 (AMPA PAM) - CIAS Phase 2

Emerging Growth Areas Immunology Dapirolizumab pegol (anti-CD40L)* - SLE Phase 3

BIIB059 (anti-BDCA2) - CLE/SLE Phase 2

Acute Neurology BIIB093 (glibenclamide IV) - LHI ^ Stroke

TMS-007 # - Acute Ischemic Stroke

Neurovascular BIIB093 (glibenclamide IV) - LHI^ Stroke Phase 3

BIIB093 (glibenclamide IV) - Brain Contusion Phase 2

BIIB131 (TMS-007) - Acute Ischemic Stroke Phase 2

Neuropathic Pain BIIB074 (vixotrigine) - Trigeminal Neuralgia Phase 2

BIIB074 (vixotrigine) - Small Fiber Neuropathy Phase 2

BIIB095 (Nav 1.7) - Neuropathic Pain Phase 1

Biosimilars SB11 (referencing LUCENTIS) *

Filed in U.S.

Genetic Neurodevelopmental Disorders BIIB121 (UBE3A ASO) # - Angelman Syndrome

Specialized Immunology Dapirolizumab pegol (anti-CD40L)* - SLE Phase 3

BIIB059 (anti-BDCA2) - SLE Phase 3

BIIB059 (anti-BDCA2) - CLE Phase 2

Biosimilars BYOOVIZ (referencing LUCENTIS®) *

SB15 (referencing EYLEA®) *

BIIB800 (referencing ACTEMRA®)* Phase 3

* Collaboration program

**Not yet commercially available

# Option agreement

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For information about certain of our agreements with collaborators and other third-parties, please read the subsection entitled Business Relationships below and Note 2, Acquisitions , Note 18, Collaborative and Other Relationships, and Note 19, Investments in Variable Interest Entities, to our consolidated financial statements included in this report.

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Business Relationships

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Below is a brief description of certain business relationships and collaborations that expand our pipeline and provide us with certain rights to existing and potential new products and technologies.

For additional information on certain of these relationships, including their ongoing financial and accounting impact on our business, please read Note 2, Acquisitions , Note 18, Collaborative and Other Relationships, and Note 19, Investments in Variable Interest Entities, to our consolidated financial statements included in this report.

For additional information on certain of these relationships, including their ongoing financial and accounting impact on our business, please read Note 18, Collaborative and Other Relationships, and Note 19, Investments in Variable Interest Entities, to our consolidated financial statements included in this report.

Acorda Therapeutics, Inc.

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in November 2019.

During the fourth quarter of 2021 VUMERITY was approved for the treatment of RRMS in the E.U., Switzerland and the U.K.

Under this agreement, we have an exclusive, worldwide license to develop and commercialize VUMERITY.

Bristol-Myers Squibb Company

We have an exclusive license agreement with Bristol-Myers Squibb Company (BMS) for the development and potential commercialization of BIIB092 (gosuranemab), a Phase 2 investigational therapy in Alzheimer's disease.

Under this agreement, we received worldwide rights to gosuranemab and are responsible for the full development and potential commercialization of gosuranemab in Alzheimer's disease.

Denali Therapeutics Inc.

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and China, we are responsible for commercialization and pay Denali tiered royalties.

In addition to the LRRK2 program, we also have an exclusive option to license two preclinical programs from Denali’s Transport Vehicle platform, including its Antibody Transport Vehicle:

In addition to the LRRK2 program, we also have an exclusive option to license two preclinical programs from Denali’s Transport Vehicle platform, including its

Antibody Transport Vehicle:

Abeta program and a second program utilizing its Transport Vehicle technology.

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Eisai Co., Ltd.

We have a collaboration agreement with Eisai to jointly develop and commercialize BAN2401, an Eisai product candidate for the potential treatment of Alzheimer's disease.

Eisai serves as the global operational and regulatory lead for BAN2401 and all costs, including research, development, sales and marketing expenses, are shared equally between us and Eisai.

If BAN2401 receives marketing approval, we and Eisai will co-promote BAN2401 and share profits equally.

We also have a collaboration agreement with Eisai to jointly develop and commercialize aducanumab (the Aducanumab Collaboration Agreement).

Under the Aducanumab Collaboration Agreement, the two companies will co-promote aducanumab with a region-based profit split and we lead the ongoing development of aducanumab.

We have a collaboration agreement with Eisai to jointly develop and commercialize lecanemab (BAN2401), an Eisai product candidate for the potential treatment of Alzheimer's disease.

Eisai serves as the global operational and regulatory lead for lecanemab and all costs, including research, development, sales and marketing expense, are shared equally between us and Eisai.

If lecanemab receives marketing approval, we and Eisai will co-promote lecanemab and share profits equally.

We also have a collaboration agreement with Eisai to jointly develop and commercialize ADUHELM (aducanumab) (the ADUHELM Collaboration Agreement).

Under the ADUHELM Collaboration Agreement, the two companies will co-promote ADUHELM with a region-based profit split and we lead the ongoing development and commercialization of ADUHELM.

We and Eisai co-promote AVONEX, TYSABRI and TECFIDERA in Japan in certain settings and Eisai distributes AVONEX, TYSABRI, TECFIDERA and PLEGRIDY in India and other Asia-Pacific markets, excluding China.

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(Roche Group)

We have collaboration arrangements with Genentech which entitle us to certain business and financial rights with respect to RITUXAN, RITUXAN HYCELA, GAZYVA, OCREVUS and other potential anti-CD20 therapies.

Ionis Pharmaceuticals, Inc.

We have an exclusive, worldwide option and collaboration agreement with Ionis relating to the development and commercialization of antisense therapeutics for up to three gene targets.

separate collaboration and license agreement with Ionis, we have an exclusive, worldwide license to develop and commercialize SPINRAZA for the treatment of SMA.

We also have a 10-year exclusive collaboration agreement with Ionis to develop novel ASO drug candidates for a broad range of neurological diseases.

In addition, we have research collaboration agreements with Ionis under which both companies perform discovery level research and will develop and commercialize new ASO drug candidates for the potential treatment of SMA and additional antisense or other therapeutics for the potential treatment of neurological diseases.

Under a separate collaboration and license agreement with Ionis, we have an exclusive, worldwide license to develop and commercialize SPINRAZA for the treatment of SMA.

We also have a 10-year exclusive collaboration agreement with Ionis to develop novel antisense oligonucleotide (ASO) drug candidates for a broad range of neurological diseases.

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or other therapeutics for the potential treatment of neurological diseases.

InnoCare Pharma Limited

We have a collaboration and license agreement with InnoCare for orelabrutinib, an oral small molecule Bruton's tyrosine kinase inhibitor for the potential treatment of MS.

Orelabrutinib is currently being studied in a multi-country, placebo-controlled Phase 2 trial in relapsing-remitting MS.

Neurimmune SubOne AG

We have a collaboration and license agreement with Neurimmune SubOne AG (Neurimmune) for the development and commercialization of antibodies for the potential treatment of Alzheimer's disease, including aducanumab (as amended, the Neurimmune Agreement).

We are responsible for the development, manufacturing and commercialization of all licensed products.

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Under this agreement, we are commercializing BENEPALI, an etanercept biosimilar referencing ENBREL, IMRALDI, an adalimumab biosimilar referencing HUMIRA, and FLIXABI, an infliximab biosimilar referencing REMICADE, in certain countries in Europe.

In December 2019 we completed a transaction with Samsung Bioepis and secured the exclusive rights to commercialize two potential ophthalmology biosimilar products, SB11, a proposed ranibizumab biosimilar referencing LUCENTIS, and SB15, a proposed aflibercept biosimilar referencing EYLEA, in major markets worldwide, including the U.S., Canada, Europe, Japan and Australia.

We also acquired an option to extend our existing commercial agreement with Samsung Bioepis for BENEPALI, IMRALDI and FLIXABI in certain countries in Europe and obtained an option to acquire exclusive rights to commercialize these products in China.

In addition to our joint venture and commercialization agreements with Samsung Bioepis, we license certain of our proprietary technology to Samsung Bioepis in connection with Samsung

Bioepis' development, manufacture and commercialization of its biosimilar products.

In January 2022 we entered into an agreement to sell to Samsung Biologics our equity in Samsung Bioepis.

We would also be eligible to receive up to an additional $50.0 million upon the achievement of certain commercial milestones.

In December 2019 we completed a transaction with Samsung Bioepis and acquired an option to extend our existing commercial agreement with Samsung Bioepis for BENEPALI, IMRALDI and FLIXABI in certain countries in Europe.

We have also secured the exclusive rights to commercialize BYOOVIZ, a ranibizumab biosimilar referencing LUCENTIS, which was approved in the U.S., the E.U.

during the third quarter of 2021.

In addition to our joint venture and commercialization agreements with Samsung Bioepis, we license certain of our proprietary technology to Samsung Bioepis in connection with Samsung Bioepis' development, manufacture and commercialization of its biosimilar products.

Sage Therapeutics, Inc.

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Our current and contemplated activities and the products, technologies and processes that result from such activities are subject to substantial government regulation.

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Regulation of Pharmaceuticals

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Failure to register a trial or disclose study results within the required time periods could result in penalties, including civil monetary penalties.

Clinical trial programs must establish efficacy, determine an

appropriate dose and dosing regimen and define the conditions for safe use.

Clinical trial programs must establish efficacy, determine an appropriate dose and dosing regimen and define the conditions for safe use.

This is a high-risk process that requires stepwise clinical studies in which the candidate product must successfully meet predetermined endpoints.

The results of the preclinical and clinical testing of a product are then submitted to the FDA in the form of a BLA or a New Drug Application (NDA).

The results of the preclinical and clinical testing of a product are then submitted to the FDA in the form of a BLA or a NDA.

In response to a BLA or NDA, the FDA may grant marketing approval, request additional information or deny the application if it determines the application does not provide an adequate basis for approval.

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• Accelerated Approval :

The FDA may grant “accelerated approval” to products that treat serious or life-threatening illnesses and that provide meaningful therapeutic benefits to patients over existing treatments.

The FDA may grant “accelerated approval” to products that treat serious or life-threatening illnesses and that

provide meaningful therapeutic benefits to patients over existing treatments.

Under this pathway, the FDA may approve a product based on surrogate endpoints or clinical endpoints other than survival or irreversible morbidity.

When approval is based on surrogate endpoints or clinical endpoints other than survival or morbidity, the sponsor will be required to provide the FDA with confirmatory data post-approval to verify and describe clinical benefit.

Under the FDA's accelerated approval regulations, if the FDA concludes that a drug that has been shown to be effective can be safely used only if distribution or use is restricted, it may require

certain post-marketing restrictions to assure safe use.

Under the FDA's accelerated approval regulations, if the FDA concludes that a drug that has been shown to be effective can be safely used only if distribution or use is restricted, it may require certain post-marketing restrictions to assure safe use.

In addition, for products approved under accelerated approval, sponsors may be required to submit all copies of their promotional materials, including advertisements, to the FDA at least 30 days prior to initial dissemination.

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“Priority review” only applies to applications (original or efficacy supplement) for a drug that treats a serious condition and, if approved, would provide a significant improvement in safety or effectiveness of the treatment, diagnosis or prevention of a serious condition.

Priority review may also be granted for any supplement that proposes a labeling change due to studies completed in response to a written request from the FDA for pediatric studies, for an application for a drug that has been designated as a qualified infectious disease product or for any application or supplement for a drug submitted with a priority review voucher.

Priority review may also be granted for

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any supplement that proposes a labeling change due to studies completed in response to a written request from the FDA for pediatric studies, for an application for a drug that has been designated as a qualified infectious disease product or for any application or supplement for a drug submitted with a priority review voucher.

In December 2016 the FDA issued a rare pediatric disease priority review voucher to us in connection with the approval of SPINRAZA.

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APPROVAL OF CHANGES TO AN APPROVED PRODUCT

If we seek to make certain types of changes to an approved product, such as adding a new indication, making certain manufacturing changes or changing manufacturers or suppliers of certain ingredients or components, the FDA will need to review and approve such changes in advance.

If we seek to make certain types of changes to an approved product, such as adding a new indication, making certain manufacturing changes or

changing manufacturers or suppliers of certain ingredients or components, the FDA will need to review and approve such changes in advance.

In the case of a new indication, we are required to demonstrate with additional clinical data that the product is safe and effective for a use other than what was initially approved.

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In May 2017 new regulations governing medical devices (MDR) and in-vitro diagnostic medical devices (IVDR) entered into force in the E.U.

although these are not expected to fully apply until May 2021 with respect to the MDR regulations and May 2022 with respect to the IVDR regulations.

The MDR became applicable in May 2021.

The IVDR regulations are not expected to fully apply until May 2022.

All products covered by these regulations will be required to comply with them at the end of the transitional periods.

These regulations introduce new requirements, including for clinical investigation of certain classifications of medical devices, require increased regulatory scrutiny, enhance the requirements for post market surveillance and vigilance and provide for greater transparency.

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vigilance and provide for greater transparency.

These regulations also change the requirements for assessment of the medical device components of integral drug-device combination products, necessitating assessment of the device components under both the medical device and medicinal product regulatory regimes.

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The marketing authorization application is similar to the NDA or BLA in the U.S.

and is evaluated by the Committee for Medicinal Products for Human Use (CHMP), the expert scientific committee of the EMA responsible for human medicines.

and is evaluated by the CHMP, the expert scientific committee of the EMA responsible for human medicines.

If the CHMP determines that the marketing authorization application fulfills the requirements for quality, safety and efficacy and that the medicine has a positive benefit risk balance, it will adopt a positive opinion recommending the granting of the marketing authorization by the EC.

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The centralized procedure is required for all biological products, orphan medicinal products and new treatments for neurodegenerative disorders, and it is available for certain other products, including those which constitute a significant therapeutic, scientific or technical innovation.

In addition to the centralized procedure, the European regulatory framework includes the following options for regulatory review and approval in E.U.

In addition to the centralized procedure, the European regulatory framework includes the following options for regulatory review and approval in the E.U.

member states:

• a national procedure, where the first application is made to the competent authority in one E.U.

country only;

member state only;

• a decentralized procedure, where applicants submit identical applications to several E.U.

countries and receive simultaneous approval, if the medicine has not yet been authorized in any E.U.

member states and receive simultaneous approval, if the medicine has not yet been authorized in any E.U.

member state;

• a mutual recognition procedure, where applicants that have a medicine authorized in one E.U.

country can apply for mutual recognition of this authorization in other E.U.

member state can apply for mutual recognition of this authorization in other E.U.

member states

As in the U.S., the E.U.

also has distinct approaches intended to optimize the regulatory pathways for therapeutically important drugs, including the Priority Medicines Evaluation Scheme (PRIME), accelerated assessment and conditional marketing authorization.

PRIME is intended to provide additional support to medicine developers throughout the

development process.

also has distinct approaches intended to optimize the regulatory

pathways for therapeutically important drugs, including the Priority Medicines Evaluation Scheme (PRIME), accelerated assessment and conditional marketing authorization.

PRIME is intended to provide additional support to medicine developers throughout the development process.

Regulatory review timelines in the E.U.

may be truncated under accelerated assessment for products that address an unmet medical need.

In addition, conditional marketing authorizations may be granted for such products in the interest of public health, where the benefit of immediate availability outweighs the risk of less comprehensive data than normally required.

In addition, conditional marketing authorizations may be granted for products in the interest of public health, where the benefit of immediate availability outweighs the risk of having less comprehensive data than normally required.

Conditional marketing authorizations are valid for one year and can be renewed annually.

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Aside from the U.S.

and E.U., there are countries in other regions where it is possible to receive an "accelerated" review whereby the national regulatory authority will commit to truncated review timelines for products that meet specific medical needs.

and the E.U., there are countries in other regions where it is possible to receive an "accelerated" review whereby the national regulatory authority will commit to truncated review timelines for products that meet specific medical needs.

there is detailed legislation on pharmacovigilance and extensive guidance on good pharmacovigilance practices.

A failure to comply with E.U.

A failure to comply with the E.U.

pharmacovigilance obligations may result in significant financial penalties for the marketing authorization holder.

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Marketing authorization holders have an obligation to inform regulatory agencies of any new information which may influence the evaluation of benefits and risks of the medicinal product concerned.

In the U.S., E.U.

In the U.S., the E.U.

and other jurisdictions, regulatory agencies, including the FDA, conduct periodic inspections of NDA, BLA and marketing authorization holders to assess their compliance with pharmacovigilance obligations.

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Good Manufacturing Practices

Regulatory agencies regulate and inspect equipment, facilities and processes used in the manufacturing and testing of pharmaceutical and biologic products prior to approving a product.

If, after receiving approval from regulatory agencies, a

company makes a material change in manufacturing equipment, location or process, additional regulatory review and approval may be required.

If, after receiving approval from regulatory agencies, a company makes a material change in manufacturing equipment, location or process, additional regulatory review and approval may be required.

We also must adhere to current Good Manufacturing Practices (cGMP) and product-specific regulations enforced by regulatory agencies following product approval.

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Failure of such third-parties to comply with cGCP can likewise result in rejection of our clinical trial data or other sanctions.

In April 2014 the EC adopted a new Clinical Trial Regulation, which was effective in June 2014 but is not expected to apply until 2021.

In April 2014 the EC adopted a new Clinical Trial Regulation, which was entered into force in June 2014 but will not apply until January 2022.

There are transitional provisions for clinical trials which are ongoing at the date of application.

Clinical trial applications may also continue to be made under the Clinical Trial Directive (the existing regulatory framework) until January 2023.

All clinical trials must fully comply with the Clinical Trial Regulation by January 2025.

The regulation harmonizes the procedures for assessment and governance of clinical trials throughout the E.U.

and will require that information on the authorization, conduct and results of each clinical trial conducted in the E.U.

and will require that

information on the authorization, conduct and results of each clinical trial conducted in the E.U.

be publicly available.

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The Patient Protection and Affordable Care Act (PPACA) amended the Public Health Service Act (PHSA) to authorize the FDA to approve biological products, referred to as biosimilars or follow-on biologics, that are shown to be "highly similar" to previously approved biological products based upon potentially abbreviated data packages.

The biosimilar

must show it has no clinically meaningful differences in terms of safety and effectiveness from the reference product, and only minor differences in clinically inactive components are allowable in biosimilar products.

The biosimilar must show it has no clinically meaningful differences in terms of safety and effectiveness from the reference product, and only minor differences in clinically inactive components are allowable in biosimilar products.

The approval pathway for biosimilars does, however, grant a biologics manufacturer a 12-year period of exclusivity from the date of approval of its biological product before biosimilar competition can be introduced.

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Orphan Drug Act, the FDA may grant orphan drug designation to drugs or biologics intended to treat a “rare disease or condition,” which generally is a disease or condition that affects fewer than 200,000 individuals in the U.S.

If a product which has an orphan drug designation subsequently receives an initial FDA approval for the indication for which it has such designation, the product is entitled to orphan exclusivity, i.e., the FDA may not approve any other applications to market the same drug for the same indication for a period of seven years following marketing approval, except in certain very limited circumstances, such as if the later product is shown to be clinically superior to the orphan product.

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following marketing approval, except in certain very limited circumstances, such as if the later product is shown to be clinically superior to the orphan product.

Legislation similar to the U.S.

Orphan Drug Act has been enacted in other countries to encourage the research, development and marketing of medicines to treat, prevent or diagnose rare diseases.

In the E.U., medicinal products that receive and maintain an orphan designation are entitled to 10 years of market exclusivity following approval, protocol assistance and access to the centralized procedure for marketing

authorization.

SPINRAZA has been granted orphan drug designation in the U.S., E.U.

SPINRAZA has been granted orphan drug designation in the U.S., the E.U.

Regulation Pertaining to Pricing and Reimbursement

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The requirements for calculating AMP and best price are complex.

We are required to report any revisions to AMP or best price previously reported within a certain period, which revisions could affect our rebate liability for prior quarters.

We are required to report any

revisions to AMP or best price previously reported within a certain period, which revisions could affect our rebate liability for prior quarters.

In addition, if we fail to provide information timely or we are found to have knowingly submitted false information to the government, the statute governing the Medicaid Drug Rebate Program provides for civil monetary penalties.

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If a manufacturer is found to have made a misrepresentation in the reporting of ASP, the governing statute provides for civil monetary penalties.

In November 2020 CMS issued an interim final rule that seeks to lower prescription drug costs by paying no more for certain Medicare Part B drugs than the lowest price paid for such drugs in certain other countries (the "most favored nation" rule).

One of the drugs subject to the rule is TYSABRI.

Under the rule, the lower payment rates for affected drugs would be phased in over a period of four years, beginning in 2021.

Although the rule is being challenged by industry associations on a number of grounds, if the challenges are unsuccessful, the rule could harm our business.

In addition, if the rule were expanded to include other drugs or to include Medicare Part D, such expansions could cause additional harm.

Medicare Part D provides coverage to enrolled Medicare patients for self-administered drugs (i.e., drugs that are not administered by a physician).

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In addition, manufacturers, including us, are required to provide to the CMS a discount of up to 70.0% on brand name prescription drugs utilized by Medicare Part D beneficiaries when those beneficiaries reach the coverage gap in their drug benefits.

Legislation is pending in Congress that includes significant modifications to Medicare Part B and Medicare Part D.

Specifically, the Build Back Better Act includes provisions that would, among other things:

1) allow CMS to directly negotiate the prices of certain drugs paid for by Medicare and impose a significantly discounted maximum price;

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2) impose inflation penalties (in the form of rebates) for price increases that exceed the rate of inflation;

3) re-design the Medicare Part D benefit in a way that increases the financial liability of manufacturers.

If enacted, this legislation could harm our business.

• Federal Agency Discounted Pricing :

Our products are subject to discounted pricing when

purchased by federal agencies via the Federal Supply Schedule (FSS).

Our products are subject to discounted pricing when purchased by federal agencies via the Federal Supply Schedule (FSS).

FSS participation is required for our products to be covered and reimbursed by the Veterans Administration (VA), Department of Defense, Coast Guard and Public Health Service (PHS).

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Negotiating prices with governmental authorities can delay commercialization of our products.

Governments may use a variety of cost-containment measures to control the cost of products, including price cuts, mandatory rebates, value-based pricing and reference pricing

(i.e., referencing prices in other countries and using those reference prices to set a price).

Governments may use a variety of cost-containment measures to control the cost of products, including price cuts, mandatory rebates, value-based pricing and reference pricing (i.e., referencing prices in other countries and using those reference prices to set a price).

Budgetary pressures in many countries are continuing to cause governments to consider or implement various cost-containment measures, such as price freezes, increased price cuts and rebates and expanded generic substitution and patient cost-sharing.

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If we were subject to allegations concerning, or were convicted of violating, these laws, our business could be harmed.

Laws and regulations have been enacted by the federal government and various states to regulate the sales and marketing practices of pharmaceutical manufacturers.

Laws and regulations have been enacted by the federal government and various states to regulate the sales and marketing practices of pharmaceutical

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manufacturers.

The laws and regulations generally limit financial interactions between manufacturers and health care providers or require disclosure to the government and public of such interactions.

The laws include federal “sunshine” provisions.

The sunshine provisions apply to pharmaceutical manufacturers with products reimbursed under certain government programs and require those manufacturers to disclose annually to the federal government (for re-disclosure to the public) certain payments made to physicians and certain other healthcare practitioners or to

teaching hospitals.

State laws may also require disclosure of pharmaceutical pricing information and marketing expenditures.

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National Institutes of Health Guidelines for Research Involving Recombinant DNA Molecules (NIH Guidelines).

By local ordinance, we are required to, among other things, comply with the NIH Guidelines in relation to our facilities in Research Triangle Park (RTP), NC and are required to operate pursuant to certain permits.

By local ordinance, we are required to, among other things, comply with the NIH Guidelines in relation to our facilities in RTP, NC and are required to operate pursuant to certain permits.

Our present and future business has been and will continue to be subject to various other laws and regulations.

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The extent of government regulation, which might result from future legislation or administrative action, cannot accurately be predicted.

The European Parliament and the Council of the European Union adopted a comprehensive general data privacy regulation (GDPR) in 2016 to replace the current E.U.

The European Parliament and the Council of the E.U.

adopted a comprehensive general data privacy regulation (GDPR) in 2016 to replace the current E.U.

Data Protection Directive and related country-specific legislation.

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The GDPR also imposes strict rules on the transfer of personal data out of the E.U.

to the U.S., provides an enforcement authority and imposes large penalties for noncompliance, including the potential for fines of up to €20.0 million or 4.0% of the annual global revenues of the infringer, whichever is greater.

Environmental Matters

We strive to comply in all material respects with applicable laws and regulations concerning the environment.

While it is impossible to predict accurately the future costs associated with environmental compliance and potential remediation activities, compliance with environmental laws is not expected to require significant capital expenditures and has not had, and is not expected to have, a material adverse effect on our operations or competitive position.

Manufacturing

We seek to ensure an uninterrupted supply of medicines to patients around the world.

To that end, we continually review our manufacturing capacity,

capabilities, processes and facilities.

We believe that our manufacturing facilities, together with the third-party contract manufacturing organizations we outsource to, currently provide sufficient capacity for our products and to Samsung Bioepis, our joint venture that develops, manufactures and markets biosimilar products, and other strategic contract manufacturing partners.

To that end, we continually review our manufacturing capacity, capabilities, processes and facilities.

We believe that our manufacturing facilities, together with the third-party contract manufacturing organizations we

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outsource to, currently provide sufficient capacity for our products and to Samsung Bioepis, our joint venture that develops, manufactures and markets biosimilar products, and other strategic contract manufacturing partners.

In order to support our future growth and drug development pipeline, we are expanding our large molecule production capacity by building a large-scale biologics manufacturing facility in Solothurn, Switzerland.

We expect this facility to be partially operational during the first half of 2021.

In the second quarter of 2021 a portion of the facility received a GMP multi-product license from SWISSMEDIC.

In March 2021 we announced our plans to build a new gene therapy manufacturing facility in RTP, North Carolina to support our gene therapy pipeline across multiple therapeutic areas.

The new facility will be approximately 175,000 square feet and is expected to be operational by the end of 2023.

Construction for this new facility began during the fourth quarter of 2021.

Manufacturing Facilities

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In addition to our drug substance manufacturing facility, we have a drug product manufacturing facility and supporting infrastructure in RTP, NC, including a parenteral facility and an oral solid dose products manufacturing facility.

The parenteral facility adds capabilities and capacity for filling biologics into vials and is principally used for filling product candidates.

The parenteral facility adds capabilities and capacity for filling biologics into vials and is used for filling product candidates.

The oral solid dose products facility can supplement our outsourced small molecule manufacturing capabilities, including the manufacture of TECFIDERA.

We also have an oligonucleotide synthesis manufacturing facility in RTP, NC.

We also have an oligonucleotide synthesis manufacturing facility in RTP, North Carolina.

This facility gives us the capability to manufacture ASO drugs like SPINRAZA as well as our other ASO candidates currently in our clinical pipeline.

In order to support our future growth and drug development pipeline, we are building a large-scale biologics manufacturing facility in Solothurn, Switzerland, which we expect to be partially operational during the first half of 2021.

In order to support our future growth and drug development pipeline, we are building a large-scale biologics manufacturing facility in Solothurn, Switzerland.

In the second quarter of 2021 a portion of the facility received a GMP multi-product license from SWISSMEDIC.

Genentech is responsible for all worldwide manufacturing activities for bulk RITUXAN, RITUXAN HYCELA and GAZYVA and has sourced the manufacture of certain bulk RITUXAN, RITUXAN HYCELA and GAZYVA requirements to a third party.

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and Ionis supplies the active pharmaceutical ingredient (API) for SPINRAZA.

Alkermes currently supplies VUMERITY to us pursuant

to a supply agreement.

Alkermes currently supplies VUMERITY to us pursuant to a supply agreement.

In October 2019 we entered into a new supply agreement and amended our license and collaboration agreement with Alkermes.

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We principally use third-parties to manufacture the API and the final product for our small molecule products and product candidates, including TECFIDERA and FUMADERM, and the final drug product for our large molecule products and, to a lesser extent, product candidates.

We source all of our fill-finish and the majority of final product assembly and storage operations for our products, along with a substantial part of our label and packaging operations, to a concentrated group of third-party contract manufacturing organizations.

We source the majority of our fill-finish and all of our final product assembly and storage operations for our products, along with a substantial part of our label and packaging operations, to a concentrated group of third-party contract manufacturing organizations.

Raw materials, delivery devices, such as syringes and auto-injectors, and other supplies required for the production of our products and product candidates are procured from various third-party suppliers and manufacturers in quantities adequate to meet our needs.

Continuity of supply of such raw materials, devices and supplies is assured using a strategy of dual sourcing where possible or by a risk-based inventory strategy.

Continuity of supply of such raw materials, devices and supplies is assured through inventory management and dual sourcing as appropriate.

Our third-party service providers, suppliers and manufacturers may be subject to routine cGMP inspections by the FDA or comparable agencies in other jurisdictions and undergo assessment and certification by our quality management group.

Environmental Matters

We remain committed to reducing our environmental footprint by eliminating harmful emissions and by minimizing resources used to manufacture our products.

Since 2014 we have taken responsibility for our impact on climate change by matching 100% of our electricity usage with renewable energy, credits and offsets, driving efficiency initiatives internally and working with our suppliers.

Green chemistry is embraced throughout our company, continually exploring new ways to make our

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drug development processes safer, more efficient and more sustainable while also saving resources.

Our Executive Committee has responsibility for evaluating the impact of climate change on the business and overseeing actions taken by the company to limit its adverse impact on the environment.

In 2020 we launched our Healthy Climate, Healthy Lives initiative, which is our 20-year, $250 million initiative to address climate, health and equity.

We aim to eliminate fossil fuel emissions across our operations by 2040, engage employees and suppliers and collaborate with renowned institutions to advance the science and action to improve health outcomes.

As part of our commitment, we have tied a portion of our employees' and executive officers' 2021 compensation to advancing our Environmental, Social and Governance strategy.

We strive to comply in all material respects with applicable laws and regulations concerning the environment.

Human Capital

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do not permit us to collect ethnic or racial data on our employees.

Globally, 48%

of Biogen’s positions at director-level and above were held by women.

Globally, 47.8% of Biogen’s positions at director-level and above were held by women as of December 31, 2021.

In 2020 we introduced an updated DE&I strategy that outlines actionable steps to deepen our commitment across the business, building upon a strong foundation.

This plan includes a four-part strategy to build our talent and leadership pipeline, improve health outcomes for the African American, Black, Latinx and other minority communities in the disease areas we treat and expand sourcing with minority-owned businesses.

This plan includes a four-part strategy to build our talent and leadership pipeline, improve health outcomes for minority communities in the disease areas we treat and expand sourcing with

minority-owned businesses.

We plan to create greater awareness and capability in our organization through leadership accountability and transparency.

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We are honored to be recognized as a company of choice.

We scored 100.0% on the 2020 Disability Equality Index, which measures our policies and practices related to disability inclusion, for the third consecutive year.

Additionally, for the seventh consecutive year, we were recognized as a Best Place to Work for LGBTQ Equality by the Human Rights Campaign, scoring 100.0% on their Corporate Equality Index.

For the fourth consecutive year, we scored 100.0% on the 2021 Disability Equality Index, which measures our policies and practices related to disability inclusion.

Additionally, for the second consecutive year, we were awarded by Disability:IN North Carolina with the 2021 DI-NC Employer Award for our commitment to champion and invest in disability inclusion at the affiliate and national levels.

For the eighth consecutive year, we were recognized as a Best Place to Work for LGBTQ Equality by the Human Rights Campaign, scoring 100.0% on their Corporate Equality Index.

In 2021 we were also ranked in the top five of Fortune 500's Measure Up initiative, which highlights the most progressive companies on DE&I efforts.

In January 2021 we shared the results of a global pay equity analysis.

The analysis confirmed that fairness and equity are embedded in our compensation practices around the globe with respect to gender and additionally in the U.S.

with respect to race.

In 2021 we also committed to strengthen the DE&I awareness and capability of our employees.

We ended 2021 with close to 90.0% of people managers trained on inclusive recruiting and hiring, and a majority of global employees trained on DE&I curriculum.

Philosophy on Pay Equity

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We regularly review our compensation practices and analyze the equity of compensation decisions, for individual employees and our workforce as a whole.

If we identify employees with pay gaps, we review and take appropriate action to ensure fidelity between our stated philosophy and actions.

If we identify employees with pay gaps, we review and take action to attain fidelity between our stated philosophy and actions.

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We institute measures, such as communications and trainings, to recognize, interrupt and prevent bias in hiring, performance management and compensation decisions and we provide resources to further develop managers and leaders to help them make equitable decisions about pay.

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Managers coach employees for performance, and also engage in employee development discussions to support growth and learning.

We provide our employees access to over 8,000 on-demand learning modules in English, French, German, Spanish, Japanese and Portuguese.

We provide our employees access to over 17,000 on-demand learning modules in English, French, German, Spanish, Japanese, Portuguese and Mandarin.

Additionally, we have a wide selection of courses and trainings that are offered through Biogen University, our global validated learning management system.

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Encourages veterans and allies of veterans to connect and support one another.

Fosters awareness and appreciation of different cultural backgrounds, in addition to promoting networking and development opportunities for members.

Fosters awareness and appreciation of different cultural backgrounds, in addition

to promoting networking and development opportunities for members.

Supports a best-in-class working environment for LGBTQ employees and embraces all LGBTQ employees and their allies.

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Succession planning

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Each year we conduct a talent review across our global enterprise that includes, among other important topics, a review of succession plans for many of our roles.

To help ensure the long-term continuity of our business, we actively manage the development of

talent to fill the roles that are most critical to the on-going success of our company.

To help ensure the long-term continuity of our business, we actively manage the development of talent to fill the roles that are most critical to the on-going success of our company.

In addition, each year our Board of Directors reviews the succession plan for our executives.

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We encourage employees to collaboratively engage in proactive problem solving through practices such as Open Reporting and Work Observation and Risk Conversations.

Additionally, our physical safety program focused on detailed evaluations of critical tasks that could expose employees to serious injury or fatality if controls are absent or not used.

The actions we implement as a result of these evaluations reduce the risks associated with these essential activities and ensure our operational systems are safer and more resilient for employees.

We also utilize “After Action Reviews” following the completion of a project.

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By engaging and empowering our employees through such programs, we believe that we can help change how the entire industry approaches safety performance and risk management.

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Information about our Executive Officers (as of February 3, 2022)

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Chirfi Guindo Executive Vice President, Global Product Strategy and Commercialization 56 2017

Rachid Izzar Executive Vice President, Head of Alzheimer's and Dementia Business Unit 47 2019

Kramer Senior Vice President, Chief Accounting Officer 56 2018

Sandrock, Jr., M.D., Ph.D.

Executive Vice President, Research and Development 63 1998

Michel Vounatsos

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Vounatsos held management positions at Ciba-Geigy, a pharmaceutical company.

Vounatsos currently serves on the advisory board of Tsinghua University School of Pharmaceutical Sciences, on the Supervisory Board of Liryc, the Electrophysiology and Heart Modeling Institute at the University of Bordeaux, on the board of directors of N-Lorem Foundation and as a member of the MIT Presidential CEO Advisory Board.

Vounatsos currently serves on the advisory board of Tsinghua University School of Pharmaceutical Sciences, on the Supervisory Board of Liryc, the Electrophysiology and Heart Modeling Institute at the University of Bordeaux, as a member of the MIT Presidential CEO Advisory Board and as a member of NetZero International Leadership Counsel.

Public Company Boards

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l Boston University School of Law, J.D.

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McDonnell has served as our Executive Vice President and Chief Financial Officer since August 2020.

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McDonnell spent 14 years at PricewaterhouseCoopers LLP, including 4 years as a partner.

McDonnell has a Bachelor of Science degree in accounting from Georgetown University and is a certified public accountant.

McDonnell is a licensed certified public accountant (CPA).

l Georgetown University, B.S.

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l The George Washington University, Ph.D.

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Chirfi Guindo

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Finance/Economics

Izzar has served as our Executive Vice President, Head of Alzheimer’s Disease and Dementia Business Unit since July 2021.

Prior to that Mr.

Izzar served as our President for the Intercontinental Region, which includes Latin America, Australia, Asia, Japan, the Middle East and Africa, Turkey and Russia, and the Global Biogen Biosimilars Unit.

Prior to joining Biogen, Mr.

Izzar was a Country President for AstraZeneca in France, where his responsibilities included leadership for commercial and manufacturing operations.

He held numerous roles at his time with AstraZeneca, including the position of Global Vice President of the Cardiovascular Franchise where he contributed significantly to the development of the franchise within the North American subsidiary, as well as in Europe and China.

Prior to that, Mr.

Izzar was Vice President Strategic Transformation, also, China Portfolio for CEO based in Shanghai and Vice President Commercial International covering China, Australia, Brazil, Russia, America Latin, Asia, Turkey, the Middle East and Africa.

l University of Sherbrooke, Masters of Business Administration

l Harvard Business School, Enterprise Executive Transformation Program

Kramer has served as our Senior Vice President, Chief Accounting Officer since December 2020.

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Kramer also held partner positions in the public accounting firms of Ernst & Young LLP and Arthur Anderson LLP.

Kramer is a licensed certified public accountant (CPA) in Massachusetts.

Kramer is a licensed CPA in Massachusetts.

She is a member of the Massachusetts Society of CPAs and the American Institute of CPAs.

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l Salem State University, B.B.A.

Sandrock, Jr., M.D., Ph.D.

Sandrock has served as our Executive Vice President, Research and Development since September 2019.

Prior to that, Dr.

Sandrock served as our Chief Medical Officer from October 2017 to January 2020, as our Executive Vice President, Chief Medical Officer Neurology and Neurodegeneration from October 2015 to October 2017, as our Chief Medical Officer and Group Senior Vice President from April 2013 to October 2015 and as our Chief Medical Officer and Senior Vice President of Development Sciences from February 2012 to April 2013.

Prior to that, Dr.

Sandrock held several other senior executive positions since joining Biogen in 1998, including Senior Vice President of Neurology Research and Development and Vice President of Clinical Development, Neurology.

l Stanford University, B.A.

Human Biology

l Harvard Medical School, M.D.

l Harvard University, Ph.D.

l Massachusetts General Hospital, internship in Medicine, residency and chief residency in Neurology and clinical fellowship in Neuromuscular Disease and Clinical Neurophysiology (electromyography)

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Available Information

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Our website address is www.biogen.com.

We make available free of charge through the Investors section of our website our Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and all amendments to those reports as soon as reasonably practicable after such material is

electronically filed with or furnished to the U.S.

Securities and Exchange Commission.

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The contents of our website are not incorporated into this report.

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Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business