Q4 and Full Year 2021
Financial Results and Business Update
February 3, 2022

Non-GAAP financial information
This presentation and the discussions during this conference call include certain financial measures that were not prepared in accordance with accounting
principles generally accepted in the U.S. (GAAP), including adjusted net income, adjusted diluted earnings per share, revenue growth at constant currency,
which excludes the impact of changes in foreign exchange rates and hedging gains or losses, and free cash flow, which is defined as net flow fromoperations less capital expenditures. Additional information regarding the GAAP and Non-GAAP financial measures and a reconciliation of the GAAP to
Non-GAAP financial measures can be found on slides 61-64 of this presentation and in the Q4 2021 earnings release and related financial tables posted on
the Investors section of Biogen.com. We believe that these and other Non-GAAP financial measures provide additional insight into the ongoing economics ofour business and reflect how we manage our business internally, set operational goals, and form the basis of our management incentive programs. NonGAAP financial measures are in addition to, not a substitute for, or superior to, measures of financial performance prepared in accordance with GAAP.
We do not provide guidance for GAAP reported financial measures (other than revenue) or a reconciliation of forward-looking Non-GAAP financial measures
to the most directly comparable GAAP reported financial measures because we are unable to predict with reasonable certainty the financial impact of items
such as the transaction, integration, and certain other costs related to acquisitions or large business development transactions; unusual gains and losses;
potential future asset impairments; gains and losses from our equity security investments; and the ultimate outcome of pending significant litigation without
unreasonable effort. These items are uncertain, depend on various factors, and could have a material impact on GAAP reported results for the guidance
period. For the same reasons, we are unable to address the significance of the unavailable information, which could be material to future results.
Note regarding trademarks: ADUHELM®, AVONEX®, PLEGRIDY®, RITUXAN®, SPINRAZA®, TECFIDERA®, TYSABRI®, and VUMERITY® are registeredtrademarks of Biogen. BENEPALI™, FLIXABI™, IMRALDI™, and BYOOVIZ™ are trademarks of Biogen. The following are trademarks of the respective
companies listed: GAZYVA® and OCREVUS® – Genentech, Inc. Other trademarks referenced in this presentation are the property of their respective
owners.

2

Forward-looking statements
This presentation and the discussions during this conference call contain forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities
Litigation Reform Act of 1995, relating to: our strategy and plans; potential of, and expectations for, our commercial business and pipeline programs; capital allocation and investment strategy;
clinical development programs, clinical trials, and data readouts and presentations; risks and uncertainties associated with drug development and commercialization; regulatory discussions,submissions, filings, and approvals and the timing thereof; the potential benefits, safety, and efficacy of our and our collaboration partners’ products and investigational therapies; the anticipatedbenefits and potential of investments, collaborations, and business development activities; our future financial and operating results; 2022 financial guidance; plans relating to share
repurchases. These forward-looking statements may be accompanied by such words as “aim,” “anticipate,” “believe,” “could,” “estimate,” “expect,” “forecast,” “goal,” “intend,” “may,” “plan,”“potential,” “possible,” “prospect,” “will,” “would,” and other words and terms of similar meaning. Drug development and commercialization involve a high degree of risk, and only a small numberof research and development programs result in commercialization of a product. Results in early-stage clinical trials may not be indicative of full results or results from later stage or larger scaleclinical trials and do not ensure regulatory approval. You should not place undue reliance on these statements or the scientific data presented.
These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including: our dependence on sales from our
products; the impact of the final NCD; uncertainty of long-term success in developing, licensing, or acquiring other product candidates or additional indications for existing products; risks that the
proposed transaction with Samsung Biologics will not be completed in a timely manner or at all; the possibility that certain closing conditions to the proposed transaction will not be satisfied;uncertainty as to whether the anticipated benefits of the proposed transaction can be achieved; failure to compete effectively due to significant product competition in the markets for our
products; failure to successfully execute or realize the anticipated benefits of our strategic and growth initiatives; difficulties in obtaining and maintaining adequate coverage, pricing, andreimbursement for our products; our dependence on collaborators, joint venture partners, and other third parties for the development, regulatory approval, and commercialization of products andother aspects of our business, which are outside of our full control; risks associated with current and potential future healthcare reforms; risks related to commercialization of biosimilars; failure toobtain, protect, and enforce our data, intellectual property, and other proprietary rights and the risks and uncertainties relating to intellectual property claims and challenges; the risk that positive
results in a clinical trial may not be replicated in subsequent or confirmatory trials or success in early stage clinical trials may not be predictive of results in later stage or large scale clinical trials
or trials in other potential indications; risks associated with clinical trials, including our ability to adequately manage clinical activities, unexpected concerns that may arise from additional data or
analysis obtained during clinical trials, regulatory authorities may require additional information or further studies, or may fail to approve or may delay approval of our drug candidates; theoccurrence of adverse safety events, restrictions on use with our products, or product liability claims; risks relating to the distribution and sale by third parties of counterfeit or unfit versions of our
products; risks relating to the use of social media for our business; risks relating to technology failures or breaches; risks relating to management and key personnel changes, including attracting
and retaining key personnel; failure to comply with legal and regulatory requirements; the risks of doing business internationally, including currency exchange rate fluctuations; risks relating toinvestment in our manufacturing capacity; problems with our manufacturing processes; fluctuations in our effective tax rate; the direct and indirect impacts of the ongoing COVID-19 pandemic on
our business, results of operations, and financial condition; fluctuations in our operating results; risks related to investment in properties; the market, interest, and credit risks associated with ourinvestment portfolio; risks relating to share repurchase programs; risks relating to access to capital and credit markets; risks related to indebtedness; change in control provisions in certain of ourcollaboration agreements; environmental risks; and any other risks and uncertainties that are described in other reports we have filed with the U.S. Securities and Exchange Commission.

These statements are based on our current beliefs and expectations and speak only as of the date of this presentation. We do not undertake any obligation to publicly update any forwardlooking statements.

3

ADUHELM (aducanumab–avwa) indication and safety statement
ADUHELM is indicated for the treatment of Alzheimer’s disease. Treatment with ADUHELM should be initiated in patients with mild cognitive impairment or mild dementia stageof disease, the population in which treatment was initiated in clinical trials. There are no safety or effectiveness data on initiating treatment at earlier or later stages of thedisease than were studied. This indication is approved under accelerated approval based on reduction in amyloid beta plaques observed in patients treated with ADUHELM.
Continued approval for this indication may be contingent upon verification of clinical benefit in a confirmatory trial or trials.
ADUHELM can cause serious side effects including amyloid related imaging abnormalities or ARIA. ARIA is a common side effect that does not usually cause any symptoms
but can be serious. ADUHELM can cause serious allergic reactions. The most common side effects include ARIA, headache and fall.
Please see full prescribing information and patient medication guide including warnings and precautions at ADUHELM.com.

ADUHELM Medication Guide. Cambridge, MA: Biogen

4Q4 2021 earnings call agenda
Introduction
Overview
R&D Update

Michael Hencke
Head of Investor Relations

Michel Vounatsos
Chief Executive Officer

Priya Singhal, M.D., M.P.H.
Interim Head of Research & Development

Financial Update

Michael McDonnell

Closing Remarks

Michel Vounatsos

Also available for Q&A

Chief Financial Officer

Chief Executive Officer

Alisha Alaimo
President, U.S. Organization
5Overview
Michel Vounatsos
Chief Executive Officer

6

Q4 and full year 2021 financial results
Total Revenues ($M)
Q4

Non-GAAP Diluted EPS ($)

Full Year

Q4

Full Year

$3.39$13,445$2,853$24.13$10,982$2,734$19.22($1.05)

2020

2021

2020

2021

2020*

2021

2020*

2021

Our GAAP financial measures and a reconciliation of GAAP to Non-GAAP financial results are at the end of this presentation.
*Beginning in the second quarter of 2021 material upfront payments and premiums paid on the acquisition of common stock associated with significant collaboration and licensing
arrangements along with the related transaction costs incurred are no longer excluded from Non-GAAP research and development expense and selling, general and administrative expense.
Non-GAAP financial results for 2020 have been updated to include the $1,084.0 million payment related to our collaboration with Sage Therapeutics, Inc. recorded in the fourth quarter of
2020, the $601.3 million payment related to our collaboration with Denali Therapeutics, Inc. recorded in the third quarter of 2020 and the $208.0 million payment related to our collaboration
with Sangamo Therapeutics, Inc. recorded in the second quarter of 2020 along with the associated transaction costs and income tax effect.

7

Proposed National Coverage Determination
Biogen Initiatives Underway

CMS Areas of Focus
Data on the clinicalbenefit for this class ofantibodies

Potential risk profile(ARIA)

Diversity andunderrepresentation ofminorities in all trials
within this classThree programs in place to generate post-approval efficacy
and safety data on ADUHELM❑ ENVISION Phase 4 post-marketing confirmatory study•
First patient expected to be screened in May 2022•
Aims to enroll 1,500 patients❑ ICARE-AD observational real-world Phase 4 study•
Aims to enroll 6,000 patients❑ EMBARK Phase 3b re-dosing study•
Enrolled ~1,700 patients

Committing to increase participation from traditionally
underrepresented communities❑ ENVISION and ICARE-AD aims to enroll 16% - 18% of U.S. participants fromblack/African American and Hispanic/Latino populations

Additional data could be generated over time and with higher levels of real-world drug utilization
CMS = Centers for Medicare & Medicaid Services; ARIA = amyloid related imaging abnormalities

8Four pillars to drive growth and long-term shareholder value

Neurology✓ Expanding on Biogen’s
leadership inneuroscience✓ Strong foundation with
26 programs in clinicaldevelopment across adiversified pipeline

Specialized
Immunology

Biosimilars✓ Two Phase 3 programsin lupus representing
potential first-in-classand best-in-classtherapies✓ Maintaining
commercialization ofcurrent portfolio after
expected sale of equity
stake in joint venture✓ Therapeutic area with adifferent risk profile✓ Aim to bring morebiosimilar products tomore patients in moregeographies✓ Continuing to evaluate
additional opportunities

DigitalHealth✓ Accelerating efforts to
support our commercial
and pipeline programs✓ Dedicated digital healthportfolio aiming topredict, measure andprevent disease✓ Recent collaboration
with TheraPanacea
aiming to further develop
digital health solutions
99

Biogen Digital Health Portfolio

Digital Health

PORTFOLIO
FOCUS❖ Digital Biomarkers❖ Personalized Medicine❖ Patient Pathway Improvement❖ Digital Therapeutics

VALUE
CREATIONOBJECTIVES

•
•
•
•

• 13 disclosed programs focused across clinical development andreal-world settings• 3 products in market with 6 programs in-development acrossdisease areas

Potentially improve efficiency of clinical development
Evidence and companion technologies that may enhance risk/benefit profile of Biogen therapies
Aim to expand market opportunities (screening, diagnosis, adherence, compliance)
Potential adjacent source of revenue (prescription digital therapeutics, software as a service – imaging, digital biomarkers etc.)

10Two potential waves of growth to build a multi-franchise portfolio
Wave 2
GENETICNEURODEVELOPMENTAL
PARKINSON’S DISEASE /MOVEMENT DISORDERS
LUPUS

Wave 1STROKE
DEPRESSIONNEUROPSYCHIATRY

ALZHEIMER’SALZHEIMER’SBIOSIMILARSEXPANDED BIOSIMILARSEXPANDED BIOSIMILARSSPINAL MUSCULAR ATROPHY

NEUROMUSCULARNEUROMUSCULAR

MULTIPLE SCLEROSISMULTIPLE SCLEROSISMULTIPLE SCLEROSISMULTIPLE SCLEROSISYESTERDAY

2016-2020

EARLY-MID 2020s

MID-LATE 2020s

DIGITAL HEALTH
11

11

Advancing a robust and diversified portfolio
Phase 1
Neurology

Multiple Sclerosis
Specialized
Immunology
Biosimilars

Alzheimer’s Disease
and Dementia

Phase 2Phase 3

Orelabrutinib
BIIB061
BIIB091
BIIB107
Aducanumab
Lecanemab
BIIB080
BIIB076
Tofersen

Neuromuscular Disorders
including SMA and ALS

BIIB078
BIIB100
BIIB105

Approved

32
Clinical programs today

10
Programs in Phase 3 or filed
today

BIIB124

Parkinson’s Disease andMovement Disorders

BIIB094
BIIB118
BIIB101
BIIB122

23
Zuranolone – PPD

Neuropsychiatry

Zuranolone – MDD

BIIB104
BIIB093 – LHI Stroke

Neurovascular

Neuropathic Pain
Genetic Neurodevelopmental
Specialized Immunology
Biosimilars

New clinical programs
since 2017

BIIB093 – Brain Contusion
BIIB131
BIIB074 – Trigeminal Neuralgia
BIIB074 – Small Fiber Neuropathy
BIIB121
Dapirolizumab pegol
BIIB059 – SLE
BIIB059 – CLE
BYOOVIZ (referencing LUCENTIS®)*
SB15 (referencing EYLEA®)
BIIB800 (referencing ACTEMRA®)> 30
Business development deals
since 2017

*Not yet commercially available; SMA = spinal muscular atrophy;
ALS = amyotrophic lateral sclerosis; PPD = postpartum depression;
MDD = major depressive disorder; LHI = large hemisphericinfarction; SLE = systemic lupus erythematosus; CLE = cutaneous
lupus erythematosus
12

Exercised option on mosunetuzumab
Building upon a long-standing collaboration with Genentech

mosunetuzumab

U.S. Regulatory
Filing Status• An investigational T-cell engaging bispecific antibody targeting CD20 and CD3 in development for B-cell
non-Hodgkin’s lymphoma and other therapeutic areas• If approved, mosunetuzumab has the potential to be a first-in-class CD20xCD3 T-cell engaging bispecificantibody in non-Hodgkin’s lymphoma• Granted Breakthrough Therapy Designation by the FDA in June 2020
• Genentech plans to complete a BLA submission to the FDA in the near future• Biogen will share in the operating profits and losses in the U.S. in the low to mid 30% range• Genentech will continue to lead the strategy and implementation of the program

Terms andEconomics• Biogen will have joint decision-making rights related to development and commercialization• In Q4 2021, Biogen recorded an expense of ~ $50 million related to the exercise of this option• Biogen is eligible to receive low single-digit royalties on sales outside the U.S.

BLA = Biologics License Application

13

Strong focus on execution with key expected milestones in 2022
2022 H1

2022 H2

Product Launches
ADUHELM – Ongoing
VUMERITY – E.U. Launch (~20 Countries)
BYOOVIZ – U.S. Launch (mid-year)

Regulatory Filings
Lecanemab* in Alzheimer’s disease – U.S. Filing+

Q2

Zuranolone* in MDD – U.S. Filing

H2

BIIB800* referencing ACTEMRA® – U.S. and E.U. Filing

H2

Data Readouts
Zuranolone* – Phase 3 in MDD#

Early

Zuranolone* – Phase 3 in PPD##

Mid-year

Lecanemab* – Phase 3 in Alzheimer’s disease

H2

BIIB104 – Phase 2 in CIAS
BIIB078^ – Phase 1 in C9Orf72 ALS

Mid-year
H1

Note: ADUHELM and lecanemab are being developed in collaboration with Eisai Co., Ltd.
* Collaboration program; + Eisai responsible for lecanemab regulatory filing; # Data from the CORAL Study; ## Data from the SKYLARK Study; ^ Option agreement
MDD = major depressive disorder; PPD = postpartum depression; CIAS = cognitive impairment associated with schizophrenia; ALS = amyotrophic lateral sclerosis

14
14

14

R&D Update
Priya Singhal, M.D., M.P.H.
Interim Head of Research & Development

15

Aducanumab significantly lowers plasma p-tau181• Plasma phospho tau levels are increased in Alzheimer’s disease1• ADUHELM significantly lowered plasma p-tau181, a biomarker of the hallmark tau tangles in Alzheimer’s disease, inboth Phase 3 trials in a dose- and time-dependent manner vs. placebo

Hansson et al., CTAD 2021
1 Palmqvist S, et al. JAMA. 2020;324:772–781.1* p<0.05, ** p<0.01, *** p<0.001 compared with placebo (nominal). MMRM with change from baseline as the dependent variable and with fixed effects of treatment group, categorical visit,
treatment-by-visit interaction, baseline value, baseline value by visit interaction, baseline age, and ApoE status.
p-tau = phosphorylated tau; pg/ml = picograms per milliliter; SE = standard error; MMRM = mixed model for repeated measures; ApoE = apolipoprotein E

16

Greater reduction in plasma p-tau181 is associated with lessclinical decline in EMERGE and ENGAGE

Association betweenchange in p-tau andefficacy at Week 78

Expectedcorrelation

Correlation (p-value)
EMERGE(n=514–521)

ENGAGE(n=577–581)

CDR-SB

Positive

0.11(0.0166)

0.14(0.0005)

MMSE

Negative-0.21(<0.0001)-0.15(0.0002)

ADAS-Cog13

Positive

0.17(0.0001)

0.15(0.0002)

ADCS-ADL-MCI

Negative-0.12(0.0086)-0.14(0.0010)p-tau181

Source: Hansson et al., CTAD 2021
Correlations are partial Spearman correlations assessed in pooled low and high dose aducanumab-treated groups, adjusting for baseline p-tau, baseline clinical endpoint, and age.
p-tau = phosphorylated tau; CDR-SB = Clinical Dementia Rating–Sum of Boxes; MMSE = Mini-Mental State Examination; ADAS-Cog 13 = Alzheimer’s Disease Assessment Scale–Cognitive
Subscale; ADCS-ADL-MCI = Alzheimer’s Disease Cooperative Study–Activities of Daily Living Inventory (mild cognitive impairment version)

17

Biogen is advancing an industry leading Alzheimer’s portfolio
Program

TargetModality

Aducanumab(ADUHELM)*

Amyloid-β

mAb

Lecanemab/BAN2401*

Amyloid-β

mAb

BIIB080#

Tau

ASO

BIIB076##

Tau

mAb

BIIB113

OGA

Small
molecule

Undisclosed asset

Amyloid-β-

Undisclosed assets

Amyloid-β

mAb

ATV-Amyloid-β**Amyloid-β

mAb

Undisclosed assets

Genetically
Validated
Targets

mAb

Undisclosed asset

Preclinical

Phase 1

Phase 2Phase 3MarketedPhase 3 readout
anticipated in H2 2022

Phase 2 start
anticipated in mid-2022

Phase 1 start
anticipated in Q1 2022

Small
molecule* collaboration with Eisai; # collaboration with Ionis; ## collaboration with Neurimmune; ** collaboration with Denali
mAb = monoclonal antibody; ASO = antisense oligonucleotide; OGA = O-GlcNAcase

18

Zuranolone has shown improvement in depressive symptoms

0

ROBIN1n=74 n=74

LANDSCAPE (MDD)
MDD-201B2
n=45 n=44

MOUNTAIN3
n=163 n=157

NEST (PPD)

WATERFALL
n=263 n=264

-4
-3.5

-8

-5.8

-12
-16

-6.8

-6.7

*

-8.3
*

-9.8

-9.8
*

-12.5
*

-20
-24

Day 2/3

Zuranolone 30 mg

HAMD-17 total score CFB, LSM (±SE)

HAMD-17 total score CFB, LSM (±SE)

NEST (PPD)

0

ROBIN1n=74 n=73

LANDSCAPE (MDD)
MDD-201B2
n=42 n=42

MOUNTAIN3
n=153 n=141

WATERFALL
n=248 n=251

-4
-8
-12

-10.3

-16
-20

-12.3
-14.1

-13.6

*

-17.8

-17.4

*

*

-24

Zuranolone 50 mg-12.5 -11.1

Day 15(Primary endpoint)

Placebo

The clinical trials above differ in sample size, patient population, entry criteria, study sites as well as other design elements. No direct comparison can be made across these clinical trials based on the graph above. ROBIN
enrolledpatients is
with
PPD;
MDD-201B,
MOUNTAIN,with
andSage
WATERFALL
enrolled
Note:zuranolone
being
developed
in collaboration
Therapeutics,
Inc. patients with MDD. Studies with Day 3 data: ROBIN, MOUNTAIN, WATERFALL; Study with Day 2 data: MDD-201B.
Source: Brown, ECNP 2021
*p<0.05 vs placebo. p values for Day2/3 LSM treatment difference are not adjusted for multiplicity and for WATERFALL is nominal.
PPD = postpartum depression; MDD = major depressive disorder; n = number of patients at that visit; HAMD-17 = 17-item Hamilton Rating Scale for Depression total score; CFB = change from baseline; LSM = leastsquares mean; SE = standard error.
1. Deligiannidis KM et al. JAMA Psychiatry. 2021 Sep 1;78(9):951-959. 2. Gunduz-Bruce H et al. N Engl J Med. 2019;381(10):903-911. 3. Mittal A, et al. Poster presented at the American Academy of Neurology Annual
Meeting. Toronto, Canada. April 25-May 1, 2020.

19

Zuranolone clinical development program provides multiple
opportunities across the depression landscape
Zuranolone as a monotherapy or adjunctive to stable ADT in MDD• 3 positive clinical studies – improvement in depressive symptoms observed as early as Day 3

and a consistent safety profile• SHORELINE study: ~ 80% of patients who responded to the initial 50mg course needed at

MAJOR
DEPRESSIVEDISORDER

most one additional treatment during their time in the one-year study• WATERFALL study: improvements in depression symptoms observed when elevated anxiety

is – or is not – present*• New Drug Application in MDD to the FDA planned in H2 2022, with rolling submission

expected to start in early 2022

Zuranolone when co-initiated with ADT in MDD• CORAL Phase 3 study expected to readout in early 2022

POSTPARTUM
DEPRESSION

Zuranolone as a monotherapy or adjunctive to stable ADT in PPD• Positive Phase 3 ROBIN study in PPD• SKYLARK Phase 3 study expected to readout in mid-2022

Zuranolone was generally well tolerated in clinical studies to date. The most common treatment-emergent adverse
events observed with zuranolone across the program were somnolence, dizziness, headache, and sedation.
Note: zuranolone is being developed in collaboration with Sage Therapeutics, Inc.
* Anxious depression was evaluated as a post hoc analysis in the WATERFALL Phase 3 study
ADT = antidepressant therapy; MDD = major depressive disorder; PPD = postpartum depression

20

Phase 2a study of BIIB131 in Acute Ischemic Stroke demonstrated positive
impacts on blood vessel reopening and patient functional recovery
Vessel Recanalization*• Treatment: 52 patients were treated with BIIB131 up to 12 hours

MRA at Baseline

after the onset of stroke symptoms - average time to treatment
was 9.5 hours vs. 9.3 hours for placebo• Safety: No incidence of symptomatic intracranial hemorrhage• Recanalization: Improved recanalization rate in patients witha visible occlusion – 58.3% for BIIB131 vs. 26.7% for placebo
MRA at 24 hours• Functional Recovery: Significant improvement in patientfunctional recovery as measured by modified Rankin Scale, ameasure of independence in daily living

BIIB131 has the potential to be a next generation
thrombolytic with an improved benefit-risk profile*Illustrative case of 78-year-old male with occlusion of right middle cerebral branch artery, NIHSS score of 9, randomized to BIIB131, 3 mg/kg cohort. Time to treatment: 8.5 hours post-stroke;
90-day outcome: mRS of 1 (No significant disability, despite symptoms; able to perform all usual duties and activities)
MRA = magnetic resonance angiopathy; NIHSS = National Institutes of Health stroke scale; mg/kg = milligrams per kilogram; mRS = Modified Rankin Score

21

Biogen is advancing a late-stage pipeline in Lupus
ProgramModality

Indication

Dapirolizumab Pegol*

Anti-CD40L mAb

SLE

BIIB059

Anti-BDCA2 mAb

SLE

BIIB059

Anti-BDCA2 mAb

CLE

Undisclosed

Small Molecule

SLE

SLE: Lupus impacting multiple organs•

Increased risk of premature death (including infections andPreclinical

Multiple, varied organs and symptoms,2 including in skin,heart, brain, lungs, joints and kidneys•

Dapirolizumab and BIIB059 represent potential first-inclass molecules for SLE

Phase 2Phase 3

CLE: Skin-based form of lupus•

Symptoms including photosensitivity, rash, pain, and pruritis(itch)3,4•Skin damage, including scarring and skin atrophy, occurs insome chronic forms4•

Most individuals with CLE may not develop systemic
manifestations5•

No biologics approved specifically for CLE

thrombotic/renal events)1•

Phase 1

*Dapirolizumab Pegol is being developed in collaboration with UCB
1. Yurkovich M, et al. Arthritis Care Res (Hoboken). 2014;66(4):608-616. 2. Crampton SP, et al. Dis Model Mech. 2014;7(9):1033-1046. 3. Ogunsanya ME, et al. Int J Womens Dermatol.
2018;4(3):152-158. 4. Ribero S, et al. Clin Rev Allergy Immunol. 2017;53(3):291-305. 5. Tebbe B, Orfanos CE. Lupus. 1997;6(2):96-104.
mAb = monoclonal antibody; SLE = systemic lupus erythematosus; BDCA2 = blood dendritic cell antigen 2; CLE = cutaneous lupus erythematosus

22BIIB059 clinical development suggests promising efficacy inskin manifestation in Phase 2
Percent change in CLASI-A Score from baseline
to week 16*

CLASI-50 Response Rate^

Source: Werth et al., ACR 2020
*Mixed effect model repeat measurement^CLASI-50 = ≥ 50% improvement from baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity score; Based on generalized linear regression adjusted fortreatment, discoid lupus erythematosus (Yes/No), and baseline Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity score (≤10 vs. >10), using a logit link function (logistic
regression) for the odds ratios and p-values, and using an identity link function (linear probability model) for the least squares (LS) means and LS mean differences. NOTE: This endpoint was not
powered for statistical significance; p-values are presented as a reference and should be interpreted in combination with the sample size.

23Advancing a robust and diversified portfolio
Phase 1

Multiple Sclerosis

Alzheimer’s Disease
and Dementia

Neuromuscular
DisordersParkinson’s Disease andMovement Disorders

Neuropsychiatry
Neurovascular
Neuropathic Pain
Genetic Neurodev.

Specialized Immunology

Biosimilars

Orelabrutinib (BTK inhibitor)* – MS
BIIB061 (oral remyelination) – MS
BIIB091 (BTK inhibitor) – MS
BIIB107 (anti-VLA4) – MS
Aducanumab (Aβ mAb)* – Alzheimer’s
Lecanemab (Aβ mAb)* – Alzheimer’s
BIIB076 (anti-tau mAb) – Alzheimer’s
BIIB080 (tau ASO) – Alzheimer’s
Tofersen (SOD1 ASO) – ALS
BIIB078 (IONIS-C9Rx)# – ALS
BIIB105 (ataxin-2 ASO)# – ALS
BIIB100 (XPO1 inhibitor) – ALS
BIIB124 (SAGE-324)* – ET
BIIB094 (ION859)# – Parkinson’s
BIIB118 (CK1 inhibitor) – ISWRD in PD
BIIB101 (ION464)# – MSA
BIIB122 (DNL151)* – Parkinson’s
Zuranolone (GABAA PAM)* – PPD
Zuranolone (GABAA PAM)* – MDD
BIIB104 (AMPA PAM) – CIAS
BIIB093 (glibenclamide IV) – LHI Stroke
BIIB093 (glibenclamide IV) – BC
BIIB131 (TMS-007) – AIS
BIIB074 (vixotrigine) – TN
BIIB074 (vixotrigine) – SFN
BIIB121 (UBE3A ASO)# – AS
Dapirolizumab pegol (anti-CD40L)* – SLE
BIIB059 (anti-BDCA2 mAb) –SLE
BIIB059 (anti-BDCA2 mAb) –CLE
BYOOVIZ (referencing LUCENTIS®)*
SB15 (referencing EYLEA®)*
BIIB800 (referencing ACTEMRA®)*

Phase 2Phase 3

Approved

Neurology

Specialized
Immunology

Biosimilars

New Phase 1 program: BIIB121 UBE3A ASO in
Angelman Syndrome
Expected 2022 Milestones:•

3 Regulatory Filings:• Lecanemab in Alzheimer’s disease (Q2)
• Zuranolone in MDD (H2)
• BIIB800 referencing ACTEMRA® (H2)•

5 Clinical Readouts in 2022
• Lecanemab Phase 3 in Alzheimer’s (H2)
• Zuranolone CORAL Phase 3 in MDD (Early)• Zuranolone SKYLARK Phase 3 in PPD (Mid)• BIIB104 Phase 2 in CIAS (Mid)• BIIB078 Phase 1 in C9Orf72 ALS (H1)
* Collaboration program; # Option agreement; MS = multiple sclerosis;
ASO = antisense oligonucleotide; ALS = amyotrophic lateral sclerosis;
ET = essential tremor; ISWRD = irregular sleep wake rhythm disorder;
PD = Parkinson’s disease; MSA = Multiple System Atrophy; PPD =postpartum depression; MDD = major depressive disorder; CIAS =cognitive impairment associated with schizophrenia; LHI = large
hemispheric infarction; BC = brain contusion; AIS = acute ischemic
stroke; TN = trigeminal neuralgia; SFN = small fiber neuropathy; Genetic
Neurodev. = genetic neurodevelopmental disorders; AS = Angelman
syndrome; SLE = systemic lupus erythematosus; CLE = cutaneous
lupus erythematosus
24

Financial Update
Michael McDonnell
Chief Financial Officer25

Q4 and full year 2021 financial results
Total Revenues ($M)
Q4

Non-GAAP Diluted EPS ($)

Full Year

Q4

Full Year

$3.39$13,445$2,853$24.13$10,982$2,734$19.22($1.05)

2020

2021

2020

2021

2020*

2021

2020*

2021

Our GAAP financial measures and a reconciliation of GAAP to Non-GAAP financial results are at the end of this presentation.
*Beginning in the second quarter of 2021 material upfront payments and premiums paid on the acquisition of common stock associated with significant collaboration and licensing
arrangements along with the related transaction costs incurred are no longer excluded from Non-GAAP research and development expense and selling, general and administrative expense.
Non-GAAP financial results for 2020 have been updated to include the $1,084.0 million payment related to our collaboration with Sage Therapeutics, Inc. recorded in the fourth quarter of
2020, the $601.3 million payment related to our collaboration with Denali Therapeutics, Inc. recorded in the third quarter of 2020 and the $208.0 million payment related to our collaboration
with Sangamo Therapeutics, Inc. recorded in the second quarter of 2020 along with the associated transaction costs and income tax effect.

26

Global multiple sclerosis revenue
Q42021 Highlights
Highlights

MS Revenue ($M)
Q4

• TECFIDERA decreased vs. prior year, impacted by
the entrance of multiple generics in the U.S.

Full Year• VUMERITY continued to grow

$8,678$1,806$1,789

$25

$26

$608

$486

$103

$7,088$3,841$105• E.U. approval obtained in Q4 2021 with planned
launches across ~20 markets in 2022
• TYSABRI increased 8% vs. prior year

$1,952• Interferons decreased 17% vs. prior year

$125

$39
$202

$261

$64
$845

$410
$992

Full Year 2021 Highlights

$475

$513

$1,946$2,063• TECFIDERA decreased vs. prior year, impacted by
the entrance of multiple generics in the U.S.

$378

$1,878$1,566$456• VUMERITY increased to $410 million• TYSABRI increased 6% vs. prior year

Q4-20

Q4-21
Numbers may not foot due to rounding.

2020

2021

• Interferons decreased 17% vs. prior year27
27

Global SPINRAZA revenue
SPINRAZA Revenue ($M)

Highlights

Q4

Full Year• Q4 2021 global SPINRAZA revenue decreased 12%
vs. the prior year; impacted by competition• Q4 2021 U.S. SPINRAZA revenue increased 7% vs.
$2,052
$498
$441

$788

$160

$1,905$588

Q3 2021 with favorable pricing and channel dynamics;
discontinuations moderated vs. Q3 2021

• Obtained reimbursement for SPINRAZA in China• Obtained exclusive rights to develop and commercialize$150

BIIB115, a preclinical investigational ASO

$338

$291

Q4-20

Q4-21

Numbers may not foot due to rounding.

$1,264$1,317

2020

2021
28

SPINRAZA patient dynamics
SPINRAZA Patients*

11,15011,27011,60011,76011,780

Q4-20

Q1-21

Q2-21

Q3-21

Q4-21

* Biogen data on file. Total patients across the post-marketing setting, the Expanded Access Program, and clinical trials.
29

U.S. ADUHELM
Q4 2021 Financials• $1 million revenue• Collaboration profit sharing includes a net
reimbursement of approximately $140 million
from Eisai related to the commercialization of
ADUHELM in the U.S.

Collaboration Economics & Accounting
Profit Share•

Revenue / Cost • Biogen books 100% of revenue and cost of goods soldof Goods Sold • Eisai’s share of gross margin will be reflected incollaboration profit sharing

Royalties••

Full Year 2021 Financials• $3 million revenue• Collaboration profit sharing includes a net
reimbursement of approximately $275 million
from Eisai related to the commercialization of
ADUHELM in the U.S.

Aducanumab is being developed in collaboration with Eisai Co; Ltd.

Biogen 55% / Eisai 45%

Biogen will pay Neurimmune royalties ranging from thehigh single digits to sub-teens based on annual net salesof ADUHELM
Neurimmune royalties are recorded through noncontrolling interest and not cost of goods sold, with Eisai’s
reimbursement reflected in collaboration profit sharing

SG&A
Expense•

R&D
Expense•All R&D expenditures are recorded net of Eisai’s
reimbursement within R&D expense, both before and after
regulatory approval

Commercial
LaunchMilestones•

One-time U.S. commercial launch milestone of $100 million
paid to Neurimmune in Q2 2021
After cost sharing with Eisai and taxes, net P&L impact of 30~$45 million in Q2 2021••

Prior to regulatory approval: Eisai’s reimbursement isrecorded as an offset to SG&A expense
After regulatory approval: SG&A expense recorded on agross basis, with Eisai’s reimbursement recognized incollaboration profit sharingBiosimilars revenue
Biosimilars Revenue ($M)

Highlights

Q4

$796
$197

• Q4 Biosimilars revenue increased 12% vs. prior year

Full Yearwith increased volume partially offset by pricing
pressure. Q4 2021 benefited from a one-time priceadjustment of ~$10 million$831• Biogen contributed > €2.6 billion of healthcare savingsin 2021 across Europe1

$221
$216

$233

$98

$99

• ~ 249,000 patients on Biogen biosimilar products at

$63

$54
$26

$118

$24

$134

IMRALDIFLIXABI

$482

$498

BENEPALI

end of Q4 20212

Pursuing potential new biosimilars• BYOOVIZ (LUCENTIS® biosimilar) approved in U.S.,
E.U., and U.K., with U.S. launch planned mid-2022• SB15 (EYLEA® biosimilar) currently in Phase 3• BIIB800 (referencing ACTEMRA®) expected regulatory

Q4-20

Q4-21

2020

2021

filing in the U.S. and E.U. in 2H22
1Biogen estimate, data on file.
2Includes ~115,000 patients on BENEPALI, ~94,000 patients on IMRALDI, and ~40,000

Numbers may not foot due to rounding.

patients on FLIXABI.
BYOOVIZ is being developed with Samsung Bioepis Co., Ltd.
BIIB800 is being developed with Bio-Thera Solutions, Ltd.

31

Biogen to sell equity stake in biosimilar joint venture

Biogen to sell equity stake inbiosimilar joint venture with

Biogen will maintain the commercialization rights to current antiTNF and ophthalmology portfolio while expanding ability to pursue
additional biosimilars products independently going forward

Samsung Bioepis to
Samsung Biologics for an
aggregate consideration of

Revenue• Biogen will continue to record revenue and costs
associated with the commercialization of BENEPALI,IMRALDI, and FLIXABI• Biogen will retain commercial rights to BYOOVIZ and SB15

up to $2.3 billion

Closing of this transaction iscurrently anticipated in mid2022*

Collaboration
Profit Sharing• Biogen and Samsung Bioepis commercialization
economics will remain substantially unchanged*Closing is contingent on the effectiveness of a securities registration statement filed by Samsung Biologics and satisfaction of certain regulatory and other customary closing conditions.

32

Q4 and full year 2021 revenue highlights$ in Millions

Q4 2021

Q4 2020

D Y/Y

FY 2021

FY 2020

D FY/FY

Total Product Revenues*$2,194$2,302(5%)$8,847$10,692(17%)

RITUXAN/GAZYVA Revenues

$153

$217

(29%)

$667

$1,132(41%)

OCREVUS Royalties

$261

$202

29%

$992

$845

17%

Revenues from Anti-CD20 Therapeutic Programs

$414

$419

(1%)

$1,659$1,978(16%)

Other Revenues

$126

$132

(5%)

$476

$775

(39%)

Total Revenues*$2,734$2,853(4%)$10,982$13,445(18%)

Numbers may not foot due to rounding. Percent changes represented as favorable/(unfavorable).
* Net of hedge

33

Q4 and full year 2021 financial results highlights($ in Millions except EPS, Shares in Millions)
Revenue
Cost of Sales
Gross Profit% of revenue
R&D Expense
Non-GAAP SG&A Expense
Collaboration Profit Sharing
Non-GAAP Amortization
Non-GAAP Operating Income (Loss)
Non-GAAP Other Income (Expense)
Non-GAAP Profit (Loss) Before Taxes and JV Equity
Non-GAAP Taxes
Non-GAAP Taxes %Non-GAAP JV Equity Income (Loss)
Non-GAAP Net Income (Loss)
Non-GAAP Net Income (Loss) Attributable to NonControlling Interests
Non-GAAP Net Income (Loss) Attributable to Biogen Inc.
Weighted average diluted shares used in calculating diluted EPS
Non-GAAP Diluted EPS

Q4 2021

Q4 2020*

Δ Y/Y

FY 2021

FY 2020*

Δ FY/FY$2,734$660$2,074
76%
$700
$785
($67)
$8
$649
($67)
$582
$100
17.2%
$25
$507
$7
$500
147
$3.39

$2,853$491$2,36283%$1,726$803$66$0($234)($51)($285)
($98)
34.6%
$25
($161)($0)($161)
154($1.05)

(4%)
(35%)
(12%)

$10,982$2,110$8,87281%$2,501$2,666$7$15$3,683($265)$3,418
$537
15.7%
$73
$2,954$79$2,875150$19.22$13,445$1,805$11,63987%$3,991$2,502$233$0$4,914($187)$4,727
$821
17.4%
$45
$3,951$60$3,891161$24.13

(18%)
(17%)
(24%)

59%
2%
201%
NMF
377%
(32%)
305%
(202%)
2%
414%
NMF
411%
4%
425%

37%
(7%)
97%
NMF
(25%)
(41%)
(28%)
35%
62%
(25%)
33%
(26%)
7%
(20%)

Numbers may not foot due to rounding. Percent changes represented as favorable/(unfavorable).
Our GAAP financial measures and a reconciliation of GAAP to Non-GAAP financial results are at the end of this presentation.
*Beginning in the second quarter of 2021 material upfront payments and premiums paid on the acquisition of common stock associated with significant collaboration and licensing
arrangements along with the related transaction costs incurred are no longer excluded from Non-GAAP research and development expense and selling, general and administrative expense.
Non-GAAP financial results for 2020 have been updated to include the $1,084.0 million payment related to our collaboration with Sage Therapeutics, Inc. recorded in the fourth quarter of
2020, the $601.3 million payment related to our collaboration with Denali Therapeutics, Inc. recorded in the third quarter of 2020 and the $208.0 million payment related to our collaboration
with Sangamo Therapeutics, Inc. recorded in the second quarter of 2020 along with the associated transaction costs and income tax effect.

34Balance sheet and cash flow
Balance Sheet(as of December 31, 2021)

Cash Flow(FY 2021)$4.7B

Cash and marketable securities$3.6B

Cash flow from operations

$7.3B

Debt

$0.3B

Capital expenditures$2.6B

Net debt$3.4B

Free cash flow*$1.8B

Share repurchases*Free cash flow is defined as net cash flow from operations less capital expenditures.

3535

Biogen 2022 full year financial guidance

2022 Guidance
Revenues

Non-GAAP Diluted EPS$9.7 billion to $10.0 billion$14.25 to $16.00

Please see Biogen’s Q4 2021 earnings release, available at the Investors section of Biogen’s website at investors.biogen.com, foradditional 2022 financial guidance assumptions.
Biogen may incur charges, realize gains or losses, or experience other events or circumstances in 2022 that could cause any of theseassumptions to change and/or actual results to vary from this financial guidance.
Please see slide 2 of this presentation for additional information on our use of Non-GAAP measures, including forward-looking NonGAAP financial measures.

36

Closing
Remarks
Michel Vounatsos
Chief Executive Officer

37

Significant opportunity for value creation
Leadership in Alzheimer’s disease✓ ADUHELM is the first FDA-approved treatment targeting a defining pathology of
Alzheimer’s disease✓ Continuing to invest in a leading Alzheimer’s portfolio, building on scientificlearnings from ADUHELM

Enhanced diversification✓ Expansion beyond neurology – increasing focus on specialized immunology,
biosimilars, and digital health technologies✓ Potential for pipeline to generate impactful therapies for patients suffering fromserious diseases

Strong financial position✓ Strong balance sheet✓ Significant cash flow with flexibility to allocate capital38

Note: ADUHELM and lecanemab are being developed in collaboration with Eisai Co., Ltd.

38

Biogen: Where
Science Meets
Humanity• Formed Healthy Climate, Healthy LivesTM Scientific Advisory
Council to advance research on air pollution and brain health

Environment
1st Fortune 500 to commit to go
fossil fuel free with Healthy
Climate, Healthy LivesTM• Expanded electric vehicle fleet to 13 countries and sustained
100% renewable electricity to power operations• 9th year as biotech leader on
Dow Jones Sustainability
World Index• 2021 winner of U.S. Chamberof Commerce Foundation’sBest Sustainability Program• #11 on Newsweek’s
America’s Most Responsible
Companies list

• Collaborated with Harvard and Americares to complete climate andhealth investigation with healthcare workers across 47 U.S. states

SocialAdvance a healthier, moresustainable and equitable world• Corporate Knights Global 100
Index of World's Most
Sustainable Corporations• #36 on JUST Capital's
JUST100• Celebrated 10th year of Care Deeply employee volunteer program
exceeding 14,900 hours benefitting more than 230 community groups• Strengthened commitment to DE&I data transparency by reporting
via the Bloomberg Gender Equality Index for 1st timeGovernance
Maintain oversight and improve
ESG transparency and disclosure• Advanced Responsible Supplier Program with a new tool andtracking mechanism for ESG engagement and compliance39

Questions& Answers

40

Lecanemab (Aβ mAb)
AD PIPELINEPORTFOLIOPROPOSEDMECHANISM
OF ACTION

Neurology❖ Aducanumab (ADUHELM) – Aβ mAb❖ Lecanemab (Ph3) – Aβ mAb• Lecanemab is humanized immunoglobulin G1 (IgG1) monoclonal antibody that targets Aβ• Lecanemab selectively binds to soluble Aβ aggregate species with preferential activity for Aβ protofibrils over fibrils (>10x)

CLINICAL STUDY OVERVIEW••❖ BIIB080 (Ph1) – tau ASO❖ BIIB076 (Ph1) – tau mAb

PHASE 2 CLINICAL DATA1

Study 201 Phase 2b: is a global, placebo-controlled, double-blind, parallel-group,
randomized trial with open-label extension•

Core randomization phase (n=856) with primary endpoint ADCOMS at 12
Months and key secondary endpoints (amyloid PET, ADCOMS, CDR-SB,
ADAS-cog, and fluid biomarkers) at 18 months•

GAP period of 9-59 months (average 24 months) off treatment from end ofcore phase and initiation of OLE•

OLE for up to 60 months (ongoing) with 10 mg/kg IV biweekly treatment

Clarity AD Phase 3: A Phase 3 Placebo-Controlled, Double-Blind, Parallel-Group,
18-Month Study Evaluating Lecanemab (BAN2401) in Early Alzheimer's Disease(n=1766)••

Primary endpoint CDR-SB at 18 months; Enrollment complete, follow-up
ongoing

ADCOMS•

Dose dependent reduction in amyloid PET
values (Florbetapir tracer)•

At 18 months, 10-mg/kg biweekly lecanemab
reduced brain amyloid (-0.306 SUVr units)•

Lecanemab significantly reduced amyloid
PET values across all doses and converted
subjects from amyloid positive to negativeacross most doses based on visual read•

>80% amyloid negative by visual read for 10
mg/kg IV biweekly at 18 months(Swanson, 2018)•

Dose and time dependent reduction in decline
on ADCOMS; starting at 6 months oflecanemab treatment showing a drug-placebo
difference in favor of active treatment by 30%
at 18 months in the 10 mg/kg biweekly cohort•

The rate of amyloid-related imaging
abnormalities-edema/effusion (ARIA-E), an
adverse event associated with amyloid
targeted therapies, for the 10 mg/kg biweekly
dosing was 9.9%.

Phase 3 readout anticipated in H2 2022 with potential to be the first antiamyloid antibody with full approval in Alzheimer’s disease

Current Status:• AHEAD 3-45 Phase III study in preclinical AD ongoing (n=1400)• Breakthrough designation in the U.S. with a rolling submission for
accelerated approval expected to complete in Q2 2022
1 Swanson et al., AAIC 2018
Note: Aducanumab and lecanemab are being developed in collaboration with Eisai Co., Ltd41

Tofersen (SOD1 ALS ASO)PORTFOLIO

Neurology

PROPOSEDMECHANISM
OF ACTION

ALS PIPELINE❖ Genetic ALS:
▪ Tofersen (Ph3) – SOD1 ASO▪ BIIB078 (Ph1) – C9ORF ASO❖ Broad ALS:
▪ BIIB105 (Ph1) – Ataxin2 ASO▪ BIIB100 (Ph1) – XPO1 small molecule inhibitor• Mutations in the SOD1 gene lead to accumulation of toxic SOD1 protein• Tofersen mediates RNase H-dependent degradation of SOD1 mRNA to reduce synthesis of SOD1 protein

CLINICAL STUDY OVERVIEW

PHASE 3 VALOR DATA•

• Phase 1/2 multiple-ascending-dose study data, demonstrating target
engagement and suggesting clinical effect, published in NEJM in Jul 2020
• Phase 3 VALOR study in symptomatic SOD1-ALS read out in October
2021 [NCT02623699]•• Open-label extension (OLE) study designed to evaluate the long-term
benefit/risk of tofersen is ongoing•• ATLAS study initiated in June 2021; designed to evaluate if initiation of
tofersen in pre-symptomatic SOD1 mutation carriers with biomarker
evidence of disease activity can delay onset of clinical symptoms or signsof ALS [NCT04856982]

While statistical significance was not achieved on the primary endpoint of ALSFRS-R at 6
months in VALOR, consistent trends favoring tofersen were seen across secondary
measures including CSF SOD1 (a marker of target engagement), plasma NfL (a potential
marker of neuronal degeneration), SVC (respiratory function), HHD (muscle strength), as
well as exploratory quality of life measures
These trends became more apparent with longer-term follow-up in the OLE, where
earlier initiation of tofersen led to slowing of decline in faster-progressing participants andstabilization of clinical function in slower-progressing participants
The most common adverse events (AEs) in participants receiving tofersen were proceduralpain, headache, pain in extremity, fall and back pain. In tofersen group, 5.6% discontinued
treatment due to AEs vs 0% in placebo. Serious neurologic events were reported in 4.8% of
patients, including 2 cases of myelitis (2.0%).

LS geometric mean ratio to baseline of plasma NfL

Adjusted mean (±SE) change in % predicted
SVC

Current Status:• Further analysis and dissemination of VALOR and OLE data underway• Engaged with regulators to determine next steps for the program

ALSFRS-R = revised ALS Functional Rating Scale; SAE = serious adverse event; SOD1 = superoxide dismutase 1

Miller and Cudkowicz, ANA
2021
42

Zuranolone (GABAA PAM) – Major Depressive Disorder
NEUROPSYCHIATRY PIPELINE

Neurology

PORTFOLIO❖ Zuranolone (Ph3) – MDD❖ Zuranolone (Ph3) – PPDPROPOSEDMECHANISM
OF ACTION• Zuranolone is a synthetic neuroactive steroid GABAA receptor positive allosteric modulator with novel MOA❖ BIIB104 (Ph2) – CIAS

• Zuranolone modulates both synaptic and extrasynaptic GABAA receptors and is hypothesized to impact dysregulated neuralnetworks with the aim of providing clinical benefit in depression

CLINICAL STUDY OVERVIEW

CLINICAL DATA

• The LANDSCAPE Program includes 1 Phase 2 study and 4 Phase 3 studies of zuranolone
in patients with MDD• MDD-201B:(102 patients) A Phase 2, double-blind, placebo-controlled study evaluating thesafety, tolerability, PK and efficacy of zuranolone 30 mg in the treatment of adults withmoderate to severe MDD. Study met is primary endpoint [NCT03000530]• MDD-301A (MOUNTAIN): (581 patients) A Phase 3, double-blind, placebo-controlled study
evaluating the efficacy of zuranolone 30 mg and 20mg in the treatment of adults with MDD.
Study missed the primary endpoint at Day 15, but demonstrated sig. improvements atevery earlier timepoint (Days 3, 8 and 12) and provides supportive information[NCT03672175]• MDD-301B (WATERFALL): (542 patients) a Phase 3, double-blind, placebo-controlled
study evaluating the efficacy of zuranolone 50mg in treatment of adults with MDD. Study
met its primary endpoint [NCT04442490]
Current Status:• Ongoing: MDD-303 (SHORELINE): (target 1550 patients) a Phase 3 open-label study evaluating
repeat treatments of zuranolone (up to 50 mg) over the course of one year in adults with MDD. In
Q4-2021, an interim readout of a cohort of 199 patients receiving 50 mg showed no new safety
findings. [NCT03864614]• Ongoing: MDD-305 (CORAL) (target 424 patients) a Phase 3 double-blind, placebo-controlled
study comparing the efficacy and safety of zuranolone 50 mg co-initiated with an antidepressantversus placebo co-initiated with an antidepressant in adults with MDD. [NCT04476030] Readout
expected in early 2022
• NDA filing for zuranolone in MDD expected to complete in H2 2022

Zuranolone was generally well tolerated in clinical studies to date. The most common treatmentemergent adverse events observed with zuranolone across the program were somnolence, dizziness,headache, and sedation. Among patients with MDD and PPD treated with zuranolone <5%discontinued treatment due to AEs

Note: zuranolone is being developed in collaboration with Sage Therapeutics, Inc.
CIAS = cognitive impairment associated with schizophrenia; GABAA = γ-Aminobutyric acid type A receptor ; MDD = major depressive disorder; PAM = positive allosteric modulator;
PPD = postpartum depression; AE = adverse event43

Zuranolone (GABAA PAM) – Postpartum Depression
NEUROPSYCHIATRY PIPELINE

Neurology

PORTFOLIO❖ Zuranolone (Ph3) – MDD❖ Zuranolone (Ph3) – PPDPROPOSEDMECHANISM
OF ACTION• Zuranolone is a synthetic neuroactive steroid GABAA receptor positive allosteric modulator with novel MOA profile❖ BIIB104 (Ph2) – CIAS

• Zuranolone modulates both synaptic and extrasynaptic GABAA and is hypothesized to impact dysregulated neuralnetworks with the aim of providing clinical benefit in depression

CLINICAL STUDY OVERVIEW

PHASE 3 ROBIN Data1• The NEST Program includes two Phase 3 studies ofzuranolone in patients with PPD.
• PPD-201B (ROBIN): (153 patients randomized) a Phase 3
double blind, placebo-controlled study of the efficacy, safety
and pharmacokinetics of zuranolone 30mg in adult females
diagnosed with severe PPD. Study completed in 2018 andmet its primary endpoint, demonstrating improvement in core
symptoms and supporting further development[NCT02978326]
Current Status:• Ongoing: PDD-301 (SKYLARK) - (target 192 patients) a
Phase 3 double-blind, placebo-controlled study evaluating
the efficacy and safety of zuranolone 50 mg in adult females
diagnosed with severe PPD. [NCT04442503] Readout
expected in mid-2022• NDA filing anticipated in the H1 2023

LS mean change from baseline in HAMD-17 total score. Placebo n=74, Zuranolone 30 mg n=76. p values provided for secondary endpoints
were not adjusted for multiplicity. HAMD-17 = 17-item Hamilton Depression Rating Scale; LS = least squares; SE = standard error.

Adult patients with PPD who received treatment with zuranolone 30 mg had statistically significant
improvement in depressive symptoms compared with placebo as assessed by CFB in HAMD-17 total score at
Day 15.
• Improvements in depressive symptoms were observed as early as Day 3.
• Improvements in depressive symptoms were observed to be maintained at Day 45.
The most common adverse events (≥5%) with zuranolone were somnolence (15.4% vs 11.0%, zuranolone vsplacebo), headache (9.0% vs 12.3%), dizziness (7.7% vs 5.5%), upper respiratory tract infection (7.7% vs1.4%), diarrhea (6.4% vs 2.7%), and sedation (5.1% vs 0%). One participant in the zuranolone group had an
AE of intermittent sedation leading to drug discontinuation; no other participant discontinued study drug.

Note: Zuranolone is being developed in collaboration with Sage Therapeutics, Inc.;
1 Deligiannidis et al. JAMA Psych 2021; 78(9):951-959
CIAS = cognitive impairment associated with schizophrenia; GABAA = γ-Aminobutyric acid type A receptor; MDD = major depressive disorder; PAM = positive allosteric modulator;
PPD = postpartum depression; CFB = change from baseline; AE = adverse event

44

BIIB093 (IV glibenclamide)
NEUROVASCULAR PIPELINEPORTFOLIO

Neurology

PROPOSEDMECHANISM
OF ACTION❖ BIIB093 (Ph3) – Large Hemispheric Infarction (LHI)❖ BIIB093 (Ph2) – Brain Contusion (BCN)❖ BIIB131 (Ph2) – Acute Ischemic Stroke (AIS)• BIIB093 inhibits the SUR1-TRPM4 non-selective cation channel which is upregulated in the CNS during ischemia andreduces cerebral edema• Data from Phase 2 in patients suffering from LHI demonstrated improvements in mortality at 30 days and reduction of
midline shift within 96 hours

CLINICAL STUDY OVERVIEW• A first of its kind, randomized, double-blind, placebocontrolled, parallel-group, global, Phase 3 study toevaluate BIIB093’s safety and efficacy in LHI patients

PHASE 2 CLINICAL DATA
Distribution of mRS scores at 90 days

Reduction in Midline Shift- at 72-96
hours (Tertiary Endpoint)• Study population: Acute ischemic stroke patients aged
18 to ≤ 85 years (N=768 of which n=80 are aged 70-85)
at risk of severe cerebral edema due to LHI• BIIB093 or placebo administered as intravenous (IV)infusion over 72 hours with dosing started within 10
hours of last known normal• Primary endpoint is 90 Day mRS
Current Status:• Phase 3 CHARM study ongoing [NCT02864953]]

SUR1-TRPM4 = sulfonylurea receptor 1-transient receptor potential melastatin 4• Primary endpoint: mRS score of 0–4 at 90 days without
decompressive craniectomy; OR = 1.91 did not meetstatistical significance.
• 31 subjects (70.5%) in the BIIB093 group and 28 subjects(71.8%) in the placebo group experienced SAEs. 4 SAEs ofhypoglycemia (all asymptomatic) occurred in the BIIB093
group vs. 0 in the placebo group - all resolved on the same
day with glucose supplementation and/or reduction in study
drug dose.
• Mortality at 90 days was 17% and 36% for BIIB093 andplacebo groups, respectively
45

BIIB131 (formerly TMS-007)
PORTFOLIO

Neurology

PROPOSEDMECHANISM
OF ACTION

NEUROVASCULAR PIPELINE❖ BIIB093 (Ph3) – Large Hemispheric Infarction (LHI)❖ BIIB093 (Ph2) – Brain Contusion (BCN)❖ BIIB131 (Ph2) – Acute Ischemic Stroke (AIS)• BIIB131 is a novel thrombolytic small molecule with putative dual clot-dissolving and anti-inflammatory properties, byenhancing plasminogen-fibrin binding and soluble epoxide hydrolase inhibition• Data from Phase 2a in patients with AIS demonstrated radiographic evidence of vessel recanalization, improvement inpatient functional outcomes as measured by modified Rankin Scale, and no symptomatic intracranial hemorrhage

CLINICAL STUDY OVERVIEW

PHASE 2a* CLINICAL DATA

• Phase 2a, randomized, double-blind, placebo-controlled, dose escalation
study to evaluate the safety, efficacy, PK, PD, and mechanisms of actionof BIIB131 [JapicCTI-183842]

sICH with worsening of NIHSS ≥4 points:
zero (0%) in BIIB131 groups and one (2.6%)in the placebo group• Study population: Acute Ischemic Stroke adult patients (N=90) within 12hours of symptom onset and <88 years old• BIIB131 or placebo was administered as a single IV infusion over 30
minutes; dose cohorts of 1, 3 and 6mg/kg with maximum dose of 360mg• The primary endpoint was the incidence of symptomatic intracranial
hemorrhage with NIHSS deterioration of ≥4-point at 24 hours

Current Status:• Ph 2a study completed; further clinical studies to confirm
safety and efficacy up to 24 hours of symptom onset areunder development* Study conducted by TMS Co., LTD
mRS = modified Rankin Scale; sICH = symptomatic intracranial hemorrhage; NIHSS = National Institutes of Health Stroke Scale; OR = odds ratio

46Dapirolizumab Pegol (anti-CD40L)
LUPUS PIPELINEPORTFOLIO

Specialized
Immunology

PROPOSEDMECHANISM
OF ACTION❖ Dapirolizumab Pegol (Ph3) – Systemic Lupus Erythematosus❖ BIIB059 (Ph3) – Systemic Lupus Erythematosus❖ BIIB059 (Ph2) – Cutaneous Lupus Erythematosus• Dapirolizumab pegol (DZP) is a polyethylene glycol (PEG)-conjugated anti-CD40L Fab’ fragment, lacking a functional Fc
domain• The inhibition of CD40-CD40L interactions suppresses inflammation by reducing B cell, T-cell and APC
activation, the production of pathogenic autoantibodies, and inflammatory events that can lead to organ damage accrual

CLINICAL STUDY OVERVIEW

BICLA RESULT FROM PHASE 2 STUDY1

Current Status:• Ph3 ongoing; First patient dosed August 2020
Note: Dapirolizumab is being developed in collaboration with UCB; SLE = systemic lupus erythematosus; BICLA = British Isles Lupus Assessment Groupbased Composite Lupus Assessment; TEAE = treatment-emergent adverse events

Improvement• Ph3 double-blind, multi-center, randomized, placebo-controlled, parallel group, global
study, to evaluate the efficacy and safety of DZP in patients (N=450) with moderately
to severely active SLE despite standard of care treatment. (NCT04294667)• Primary endpoint is achievement of BICLA response at week 48.
• In the Ph2 SLE study1, although the primary endpoint was not met, DZP exhibited
improvements across multiple clinical and immunological measures of diseaseactivity after 24-weeks compared with placebo• TEAEs and serious TEAEs were generally balanced across treatment groups
during the 24-week double-blind period; more upper respiratory tract infections
were observed with DZP compared with placebo (e.g., nasopharyngitis 10.2% vs4.4% and pharyngitis 8.0% vs 2.2% of patients for DZP and placebo, respectively).
• UCB/Biogen are reinforcing their commitment to the inclusion of under-represented
groups in our clinical trials. Enrollment targets have been set to reflect the prevalenceof SLE in black / African American and Hispanic communities.
1 Furie et al. Presented at EULAR in June 2019 (Madrid, Spain)

47

BIIB059 (Anti-BDCA2 mAb) – Systemic Lupus Erythematosus
PORTFOLIO

Specialized
Immunology

PROPOSEDMECHANISM
OF ACTION

LUPUS PIPELINE❖ Dapirolizumab Pegol (Ph3) – Systemic Lupus Erythematosus❖ BIIB059 (Ph3) – Systemic Lupus Erythematosus❖ BIIB059 (Ph2) – Cutaneous Lupus Erythematosus• BIIB059 is a humanized IgG1 monoclonal antibody (mAb) targeting blood dendritic cell antigen 2 (BDCA2)• BDCA2 is an inhibitory receptor exclusively expressed on subset of human immune cells plasmacytoid dendritic cells (pDC)• BIIB059 has been shown to reduce inflammatory cytokine production from pDCs, including type-I IFN. Inflammatory mediators arethought to play a major role in the pathogenesis of lupus

PHASE 2: CHANGE IN TOTALACTIVE JOINT COUNT AT WEEK
24 (Primary Endpoint)

CLINICAL STUDY OVERVIEW• Ph2 LILAC study met its primary endpoints, demonstrating astatistically significant reduction of disease activity in patientswith SLE and CLE.

PHASE 2: SLE RESPONDER INDEX4 RESPONSE RATE AT WEEK 24
OR=3.49p=0.003• Global Phase 3 TOPAZ-1 and TOPAZ-2 studies will evaluate
the efficacy and safety of BIIB059, as compared to placebo,in active systemic lupus erythematosus (SLE).

OR=2.15
p=0.063

p=0.037• BIIB059 enrollment targets are set to reflect the prevalenceof SLE in black / African American and Hispanic communities
with the aim to achieve appropriate representation in the
TOPAZ-1 and -2 studies.

Placebo (n = 56)

Current Status:• TOPAZ-1 achieved FPI in June 2021; TOPAZ-2 achieved
FPI in August 2021 [NCT04895241; NCT04961567]

OR=3.06
p=0.008

BIIB059 450 mg (n = 64)

Furie et al., ACR 2020••

Rates of adverse events in LILAC part A were similar in placebo (67.9%) and BIIB059 (59.2%) treatmentgroupsAEs in the Infections and Infestations System Organ Class occurred in 39.3% and 35.5% of participantsreceiving placebo and BIIB059, respectively

SLE = systemic lupus erythematosus; CLE = Cutaneous Lupus Erythematosus; IgG1 = Immunoglobulin G1; pDC = plasmacytoid dendritic cell; BDCA2 = blood dendritic cell antigen 2;
FPI = first patient in; IFN = Interferon48

BIIB059 (Anti-BDCA2 mAb) – Cutaneous Lupus Erythematosus

Specialized
Immunology

PROPOSEDMECHANISM
OF ACTION• BIIB059 is a humanized IgG1 monoclonal antibody (mAb) targeting blood dendritic cell antigen 2 (BDCA2)• BDCA2 is an inhibitory receptor exclusively expressed on subset of human immune cells plasmacytoid dendritic cells (pDC)• BIIB059 has been shown to reduce inflammatory cytokine production from pDCs, including type-I IFN. Inflammatory mediators arethought to play a major role in the pathogenesis of lupus

CLINICAL STUDY OVERVIEW• Ph2 LILAC study met its primary endpoints, demonstrating a statisticallysignificant reduction of disease activity in patients with SLE and CLE.
• BIIB059 demonstrated a dose response on the percent change
from baseline in the Cutaneous Lupus Erythematosus Disease
Area and Severity Index Activity (CLASI-A) score at week 16 inpeople with CLE.
• Safety and tolerability data further support the continued development of
BIIB059• Rates of adverse events in LILAC part B were similar in theplacebo (66.7%) and pooled BIIB059 (71.7%) treatment groups• AEs in the Infections and Infestations System Organ Classoccurred in 30.3% and 34.3% of participants receiving placebo and
BIIB059, respectively

Current Status:

PHASE 2: CHANGES IN CLASI-A SCORES FROMBASELINE TO WEEK 16
Percentage Change, LS Mean (SE)PORTFOLIO

LUPUS PIPELINE❖ Dapirolizumab Pegol (Ph3) – Systemic Lupus Erythematosus❖ BIIB059 (Ph3) – Systemic Lupus Erythematosus❖ BIIB059 (Ph2) – Cutaneous Lupus Erythematosus

Placebo (n = 33)
BIIB059 50 mg (n = 26)

BIIB059 150 mg (n = 25)
BIIB059 450 mg (n = 48)

0–14.5%-20–38.8%; p = 0.015–42.5%; p = 0.001–47.9%; p < 0.001

-40

-60
2

4

8

12

16

Week
Werth et al., ACR 2020

• Currently planned pivotal study start in CLE in 2022.
SLE = systemic lupus erythematosus; CLE = Cutaneous Lupus Erythematosus; IgG1 = Immunoglobulin G1; pDC = plasmacytoid dendritic cell; BDCA2 = blood dendritic cell antigen 2; FPI = first patientin; CLASI-A = Cutaneous Lupus Erythematosus Disease Area and Severity Index – Activity; IFN = Interferon

49

Biogen Digital Health
PORTFOLIO
FOCUS

Digital Health❖Digital Biomarkers❖Personalized Medicine❖Patient Pathway improvement❖Digital Therapeutics

Disease Area: Multiple Sclerosis
Programs in
Development

Stage

Focus

Description

Cleo/Aby – Digital
Companion

Launched

Monitoring & Self Management

Cleo (Aby in North America) is a digital care companion app to help people live with
Multiple Sclerosis. It provides information, tips, symptoms tracking, reminders, tailored
to individuals.

MS PATHS – Research
Network

Launched

Clinical Development & RWE;
Treatment & Decision Support;
Diagnosis

Uses advanced technologies to generate & collect standardized patient data during
routine office visits potentially resulting in a large, high definition and diverse realworld MS cohort.

MS Performance Test –Digital Biomarkers

Launched

Clinical Development & RWE;
Treatment & Decision Support

In-clinic assessment tool that aims to objectively quantify the major motor, visual, andcognitive systems, as well as quality of life and disease history for patients with MS.
HCPs can access patient results at the point of care.

Konectom MS – Digital
Biomarkers

MarketScientific
Validation

Clinical Development & RWE;
Treatment & Decision Support;
Monitoring

Smartphone-based digital measurement platform that aims to assess key neurological
functions such as cognition, fine and gross motor control, walk, quality of life andmobility in clinical studies, in-clinic or remotely. [DigiTOMS KONECT-MS ]MS Lesion Classifier –Imaging AI*

Concept &Feasibility

Clinical Development & RWE;
Treatment & Decision Support

Clinical software using machine learning model that potentially may categorize
multiple sclerosis MRI lesions by lesion type using single time point data.

*Collaboration with TheraPanacea
HCP = healthcare provider; MS = multiple sclerosis; RWE = real-world evidence; T&D = treatment and decision; MRI = magnetic resonance imaging; AI = artificial intelligence50

Biogen Digital Health
PORTFOLIO
FOCUS

Digital Health❖Digital Biomarkers❖Personalized Medicine❖Patient Pathway improvement❖Digital Therapeutics

Disease Area: Alzheimer’s Disease and Dementia
Programs indevelopment

Stage

Focus

Description

Intuition – Digital
Biomarkers

MarketScientific
Validation

Clinical Development &RWE; Primary Prevention &Screening[INTUITION Study]: Virtual, observational study leveraging the Apple Watch, iPhone,
and CANTAB battery to potentially discover digital biomarkers for MCI screening andmay track cognitive changes in adults.

AI ARIA Identification –Imaging AI

Design &Development

Clinical Development &RWE; Treatment &Decision Support

Vulcan – Digital
Companion

Concept &Feasibility

Monitoring & Self
Management

AI-squared may be integrated in radiologist workflow/PACS and aims to provide
validated, automated MRI assessment report of quantification, severity status andlocation of ARIA-H and ARIA-E events.
Potentially provide scalable solution to aid patients with MCI / AD and caregivers innavigating complex care journey and providing emotional support.

ARIA – E/H = amyloid related imaging abnormality – edema / hemorrhage; MCI = mild cognitive impairment; HCP = healthcare provider: RWE = real-world evidence; AI = artificial intelligence51

Biogen Digital Health
PORTFOLIO
FOCUS

Digital Health❖Digital Biomarkers❖Personalized Medicine❖Patient Pathway improvement❖Digital Therapeutics

Disease Area: Neuromuscular Disorders
Programs indevelopment

Stage

Focus

Description

Konectom NMD – Digital
Biomarkers

MarketScientific
Validation

Clinical Development &RWE; Treatment &Decision Support;
Monitoring

Smartphone app that aims to assess key neurological functions such as cognition,fine and gross motor control, walk, quality of life and mobility in clinical studies, inclinic, or remotely.

Physio.me – Digital
Companion

Design &Development

Treatment & Decision
Support; Monitoring & Self
Management

Digital physiotherapy companion that offers to perform at-home, tailored, secure
exercise so NMD patients can potentially achieve their goals, measure progress andshare progress with their care team.

Capsule – VR solution

Design &Development

Treatment & Decision
SupportEvidence-based medical device that combines immersion through virtual reality
technology and medical hypnosis to potentially alleviate anxiety related to intrathecal
injection procedures.

NMD = neuromuscular diseases RWE = real world evidence; VR = virtual reality

52

Biogen Digital Health
PORTFOLIO
FOCUS

Digital Health❖Digital Biomarkers❖Personalized Medicine❖Patient Pathway improvement❖Digital Therapeutics

Disease Area: Movement Disorders
Program in
Stage
Focus
development
DiseaseArea: Movement Disorders

Description

PD Progression Score –Digital Biomarkers

PD Meaningful Progression Digital Score is a disease score enabled by a machinelearning algorithm to potentially measure change in Parkinson’s disease and its
progression.

Concept &Feasibility

Clinical Development & RWE;
Monitoring & Self Management

Disease Area: Neuropsychiatry
Program indevelopment

Stage

Focus

Description

Zephiro – Digital
Companion

Concept &Feasibility

Treatment & Decision Support;
Monitoring & Self Management

Digital patient support companion aiming to provide personalized and evidence-based
support including relapse detection to major depressive disorder care.

PD = Parkinson’s disease; RWE = real-world evidence; T&D = treatment and decision

53

BYOOVIZ™ (referencing LUCENTIS®)
Reference
Molecule

BIOSIMILARS PIPELINE❖ BYOOVIZ™ [SB11i] Approved – referencing LUCENTIS®
❖ Approvals secured by FDA, EMA, MHRA in 2H 2021

ORIGINATOR MARKET L12M Revenue (US/ROW), $M:❖ Lucentis®: $1,500M US / $2,200M ROW1

i SB11 refers to the Samsung Bioepis product candidate name

Biosimilars

PROPOSEDMECHANISM
OF ACTIONBYOOVIZ™ binds with high affinity to vascular endothelial growth factor (VEGF)-A isoforms (e.g. VEGF110, VEGF121 and VEGF165),
thereby preventing binding of VEGF-A to its receptors VEGFR-1 and VEGFR-2. Binding of VEGF-A to its receptors leads to endothelial
cell proliferation and neovascularisation, as well as vascular leakage, all of which are thought to contribute to the progression of theneovascular form of age-related macular degeneration, pathologic myopia and CNV 9 or to visual impairment caused by either diabetic
macular oedema or macular oedema secondary to retinal vein occlusion in adults.

CLINICAL STUDY OVERVIEW•

A randomized, double-blind, parallel-group, phase III study trial conducted in 75
centers in 9 countries globally from March 2018 to December 2019•

Patients with nAMD were randomized (1:1) to receive either SB11 (n=351) or
ranibizumab (Lucentis®) (n=354)•

Primary endpoints were:•

Change from baseline BCVA to BCVA at Week 8 in the FAS (for US FDA
and Korean MFDS)•

change from baseline CST to CST at Week 4 in the PPS-CST (for EMA)•

Secondary endpoints included change from baseline in BCVA, CST, CRLT, CNV
size, active CNV leakage up to week 52, in addition to safety (ocular and nonocular adverse events), immunogenicity and pharmacokinetics.

•

The safety, pharmacokinetics, and immunogenicity profiles were comparable
between treatment groups. Observed treatment-emergent adverse events (TEAEs)
were consistent with ranibizumab’s safety profile, with “intraocular pressure
increased" as the only ocular TEAE occurring in ≥5% of participants. The mostcommon non-ocular TEAEs were nasopharyngitis and hypertension. The mostfrequently reported AEs of special interest were increased intraocular pressure(SB11, 1 [0.3%]; ranibizumab, 6 [1.7%]) and iridocyclitis (SB11, 3 [0.9%]).

nAMD = neovascular age-related macular degeneration; BCVA = best corrected visual acuity; FAS = full analysis set; MFDS = Ministry of Food andDrug Safety; CST = central subfield thickness; PPS-CST = per-protocol set –CST; CNV = choroidal neovascularization; CRLT = central retinal lesion
thickness; CI = confidence interval. Note: Biosimilar indications may vary by product or region

CLINICAL DATA OVERVIEW2

Whiskers represent the 90% CI. Dashed lines represent the predefined equivalence margins of [-3 to 3 letters],

Whiskers represent the 95% CI. Dashed lines represent the predefined equivalence margin of [-36 to 36 μm],

Source: 1Evaluate/Company report MAT Q3 2021;
2 Se Joon Woo et al. JAMA Ophthalmol 2021;139:68–76

SB15 (referencing EYLEA®)
Reference
Molecule

ORIGINATOR MARKET L12M Revenue (US/ROW), $M:

BIOSIMILARS PIPELINE❖ SB15i (Ph3) – referencing EYLEA®

❖ Eylea ® $5,583 M US / $3,518 M ROW1

i SB15 refers to the Samsung Bioepis product candidate name

Biosimilars

PROPOSEDMECHANISM
OF ACTION

Vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PlGF) are members of the VEGF family of angiogenic factorsthat can act as potent mitogenic, chemotactic, and vascular permeability factors for endothelial cells. VEGF acts via two receptor tyrosine
kinases; VEGFR-1 and VEGFR-2, present on the surface of endothelial cells. PlGF binds only to VEGFR-1, which is also present on thesurface of leucocytes. Excessive activation of these receptors by VEGF-A can result in pathological neovascularisation and excessive
vascular permeability. PlGF can synergize with VEGF-A in these processes, and is also known to promote leucocyte infiltration and vascularinflammation.

CLINICAL STUDY OVERVIEW

CLINICAL DATA OVERVIEW• Randomized, double-blind, parallelgroup, phase-III study trial conducted
in 57 centers across 10 countries. Study
start July 2020; expected completion H1
2022• Patients (n=449)
with nAMD randomized (1:1) to receive
either SB15 or aflibercept (Eylea)• Primary endpoints:• change from baseline BCVA to
BCVA at Week 8• Secondary endpoints include efficacy,
safety, immunogenicity
and pharmacokinetics up to week 56
Data readout for SB15 expected not before Q4 2022
BCVA = best corrected visual acuity. Note: Biosimilar indications my vary by product or region.

Source: 1Regeneron Company reports MAT Q3 2021

BIIB800 (referencing ACTEMRA®)
Reference
Molecule

ORIGINATOR MARKET:BIOSIMILARS PIPELINE❖ BIIB800 [BAT1806i] Ph3 completed❖ Actemra® $1,727M US / $1,986M ROW1i BAT1806 refers to the Bio-Thera Solutions product candidate name

Biosimilars

PROPOSEDMECHANISM
OF ACTION• IL-6 receptor signaling activates intracellular JAK MAPK and JAK-STAT3 signaling pathways involved in several
inflammatory diseases, including Rheumatoid Arthritis.
• Tocilizumab binds to membrane-bound and soluble IL-6 receptor (IL-6R) thereby preventing IL-6 from binding to IL-6R,
inhibiting IL-6 signaling.

CLINICAL STUDY OVERVIEW

CLINICAL DATA

• Phase I: A randomized, double-blind, three-arm (reference
products RoActemra® (EU) (n=42) or Actemra® (US) (n=42),
or BIIB800 [BAT1806] n=45)), parallel-group study of a single
4 mg/kg dose administered intravenously. Healthy volunteers
were followed for 57 days for PK, immunogenicity and safety• Phase III3:• A multicenter, multinational, randomized, double-blind,parallel-group, active-control study to compare efficacy,
safety, immunogenicity, and PK of BIIB800 [BAT1806]compared with RoActemra® in 621 subjects with moderate
to severe Rheumatoid Arthritis (RA) inadequately
controlled by MTX• The study comprised a ≤ 28-day screening period, a 48week randomized treatment period, and a 4-week safety
follow-up• Phase I:• Bioequivalence study concluded that the PK, immunogenicity andsafety profile of BIIB800 [BAT1806] was similar to that of the EU/US
reference products2• Phase III:
• The study met its primary endpoints of American College of
Rheumatology 20 percent response criteria (ACR20) at Week 12(EMA) and at Week 24 (FDA, NMPA)• Biogen believes that BIIB800 [BAT1806] demonstrated equivalence inefficacy and pharmacokinetics and has a comparable safety andimmunogenicity profile to the reference product 4• Clinical data is in submission to EULAR 2022 congress; results underembargo until late May 2022 according to EULAR rules 5• Comparable safety and immunogenicity profile to the reference
product

Note: Biosimilar indications my vary by product or region.
1 Source: Roche investors finance information tool, MAT Q3 2021
2 Zhang H et al. Front Pharmacol. 2021;11:609522. doi: 10.3389/fphar.2020.609522
3 www.clinicaltrialsregister.eu/ctr-search/trial/2018-002202-31/BG.

4 https://investors.biogen.com/news-releases/news-release-details/biogen-and-bio-thera-

announce-positive-results-phase-3-study
5 https://congress.eular.org/myUploadData/files/embargo_policy_2022.pdf

Global fumarate revenue
Fumarate Revenue ($M)

Q4 2021 Highlights
Revenue vs. Q4 2020 and Q3 2021
∆Y/Y

$647

$619
$553

$578

$611

$309

$319

$326

$91

$121

and

- 1%

ROW

+ 13%

and

+ 2%

VUMERITY ROW

U.S.

- 21%

and

- 5%

VUMERITY U.S.

$124
TECFIDERA U.S.

$320

Q4-20

- 5%

TECFIDERA ROW

$39
$74

WW

$1

$288
$317

∆Q/Q

$162

$178

$179

$161

Q1-21

Q2-21

Q3-21

Q4-21

Numbers may not foot due to rounding.

57

Global interferon revenue
Interferon Revenue ($M)

Q4 2021 Highlights
Revenue vs. Q4 2020 and Q3 2021
∆Y/Y

$456
$52
$96

$48

$260

Q4-20

$400

$400

$57

$46

$47

$102

$97

$88

$33

$43

$39

$209

$214

$213

$194

Q1-21

Q2-21

Q3-21

Q4-21

Numbers may not foot due to rounding.

$388

$378
$55

PLEGRIDY
ROW$92

AVONEX
ROW

$38

∆Q/Q

WW

- 17%

and

- 3%

ROW

- 1%

and

+ 8%

U.S.

- 25%

and

- 8%

PLEGRIDYU.S.

AVONEX
U.S.

58

Global TYSABRI revenue
TYSABRI Revenue ($M)

Q4 2021 Highlights
Revenue vs. Q4 2020 and Q3 2021

$475

$204

$503

$230

$524

$224

$523

$242

∆Y/Y

$513
WW

+ 8%

and

- 2%

ROW

+ 10%

and

- 7%

U.S.

+ 6%

and

+ 2%

$225
ROW

U.S.

$271

$273

$300

$281

$288

Q4-20

Q1-21

Q2-21

Q3-21

Q4-21

Numbers may not foot due to rounding.

∆Q/Q• Biogen believes that Q4 2021 TYSABRI revenue
was positively impacted by channel dynamics inthe U.S.

59

Consolidated Statement of Income(unaudited, in millions, except per share amounts)

60

GAAP to Non-GAAP Reconciliation
Operating Expense, Other Income (Expense), net and Income Tax(unaudited, in millions, except per share amounts)
Use of Non-GAAP Financial Measures
We supplement our GAAP consolidated financial statements and GAAP financial measures with other financial measures,such as adjusted net income, adjusted diluted earnings per share, revenue growth at constant currency, which excludes
the impact of changes in foreign exchange rates and hedging gains or losses, and free cash flow, which is defined as net
flow from operations less capital expenditures. We believe that these and other Non-GAAP financial measures provide
additional insight into the ongoing economics of our business and reflect how we manage our business internally, set
operational goals and form the basis of our management incentive programs. Non-GAAP financial measures are in
addition to, not a substitute for, or superior to, measures of financial performance prepared in accordance with GAAP.

Our “Non-GAAP net income attributable to Biogen Inc.” and “Non-GAAP earnings per share - Diluted” financial measures
exclude the following items from “GAAP net income attributable to Biogen Inc.” and “GAAP earnings per share - Diluted”:
1. Acquisitions and divestitures
We exclude transaction, integration and certain other costs related to the acquisition and divestiture of businesses, theacquisitions of assets and items associated with the initial consolidation or deconsolidation of variable interest entities.
These adjustments include, but are not limited to, charges for in-process research and development and certain
milestones, the amortization and impairment of intangible assets, charges or credits from the fair value remeasurementof our contingent consideration obligations and losses on assets and liabilities held for sale.
2. Restructuring, business transformation and other cost saving initiatives
We exclude costs associated with our execution of certain strategies and initiatives to streamline operations, achievetargeted cost reductions, rationalize manufacturing facilities or refocus research and development activities. These costs
may include employee separation costs, retention bonuses, facility closing and exit costs, asset impairment charges oradditional depreciation when the expected useful life of certain assets have been shortened due to changes in anticipatedusage and other costs or credits that management believes do not have a direct correlation to our ongoing or futurebusiness operations.
3. (Gain) loss on equity security investments
We exclude unrealized and realized gains and losses and discounts or premiums on our equity security investments as we
do not believe that these components of income or expense have a direct correlation to our ongoing or future business
operations.

Footnotes referenced in the tables above are included at the end of this presentation.

4. Other items
We evaluate other items of income and expense on an individual basis and consider both the quantitative and qualitative
aspects of the item, including (i) its size and nature, (ii) whether or not it relates to our ongoing business operations and(iii) whether or not we expect it to occur as part of our normal business on a regular basis. We also include an adjustment
to reflect the related tax effect of all reconciling items within our reconciliation of our GAAP to Non-GAAP net income
attributable to Biogen Inc. and earnings per share - diluted.
61

GAAP to Non-GAAP Reconciliation
Equity Income/Loss of Investee, Noncontrolling Interests, Net Income & Diluted EPS(unaudited, in millions, except per share amounts)

Footnotes referenced in the tables above areincluded at the end of this presentation.

62

GAAP to Non-GAAP Reconciliation
Constant Currency & Free Cash Flow(unaudited, in millions)
Revenue growth at constant currency

Free cash flow

63

Notes to GAAP to Non-GAAP Reconciliation
Operating Expense & Net Income Attributable to Biogen Inc.

A For the years ended December 31, 2021 and 2020, amortization and impairment of acquired intangible assets totaled $881.3 million and $464.8 million, respectively.

During the fourth quarter of 2020 we recognized an impairment charge of $115.0 million related to BIIB111 as a result of third-party manufacturing delays that impacted thetiming and increased the costs associated with advancing BIIB111 through Phase 3 development.
In February 2021 we announced that we discontinued development of BIIB054 (cinpanemab) for the potential treatment of Parkinson's disease as our Phase 2 SPARK study
did not meet its primary or secondary endpoints. Although we made this determination in February 2021, it was based on conditions that existed as of December 31, 2020.
As a result, we recognized an impairment charge of approximately $75.4 million during the fourth quarter of 2020 to reduce the fair value of the related in-process researchand development (IPR&D) intangible asset to zero.
During the year ended December 31, 2020, amortization and impairment of acquired intangible assets reflects the impact of the BIIB111 and BIIB054 impairment charges aswell as a $19.3 million impairment charge related to one of our IPR&D intangible assets.
During the second quarter of 2021 we announced that our Phase 3 STAR study of BIIB111 and our Phase 2/3 XIRIUS study of BIIB112 did not meet their primary endpoints.
In the third quarter of 2021 we suspended further development on these programs based on the decision by management as part of its strategic review process. For the year
ended December 31, 2021, we recognized an impairment charge of $365.0 million related to BIIB111 and an impairment charge of $220.0 million related to BIIB112, reducing
the remaining book values of these IPR&D intangible assets to zero.
B For the year ended December 31, 2021, compared to the same period in 2020, we recorded a current year deferred tax benefit associated with the accelerated approval of

ADUHELM by the FDA. During the second quarter of 2021, we recorded approximately $490.0 million in a deferred tax asset related to Neurimmune SubOne AG's tax basis
in ADUHELM. The net deferred tax asset is comprised of approximately $945.0 million of gross deferred tax asset, reduced by approximately $455.0 million of unrecognizedtax benefit. During the fourth quarter of 2021 we recorded a valuation allowance of approximately $390.0 million related to this deferred tax asset. The realization of which isdependent on future sales of ADUHELM and approval of the Swiss cantonal tax authorities, with an equal and offsetting amount assigned to noncontrolling interest, resulting
in zero net impact to net income attributable to Biogen Inc.

64