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Biogen Portfolio Update

Biogen US MedicalMay 2015

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Biogen

About Biogen

Daclizumab HYPOverview of Development

SELECT

DECIDE

Anti-LINGO-1

Tysabri SPMS

Tysabri Acute Ischemic Stroke

Anti-TWEAK

Neublastin

ISIS-SMNRx

BIIB037

BAN2401

BG00011



Biogen

• Biogen is the world's oldest independent biotechnology company

• Established 1978

• Biogen has >7,500 employees worldwide and >$9.7 billion USD in annual revenues (2014)

*Pharmaceutical Industry Profile 2012, Washington DC, PhARMA, April 2012. Biogen. Available at www.biogencom.

Founded in 1978, we are the

world’s oldest independent

biotechnology company that today

has a rapidly-expanding global

footprint and employs approximately

7,000 people worldwide

Through cutting-edge science and

medicine, we discover, develop and

deliver to patients worldwide innovative

therapies for serious

neurodegenerative, hematologic and

autoimmune diseases



Approved ProductsM

ult

iple

Scl

ero

sis

Hem

op

hil

ia



Multiple Sclerosis

Alzheimer’s Disease

Acute Ischemic Stroke

Lupus Nephritis

Idiopathic Pulmonary Fibrosis

Neuropathic Pain

Spinal Muscular Atrophy

Alzheimer's Disease

Biogen Pipeline*

PHASE I PHASE II PHASE III FILED

Multiple Sclerosis

Daclizumab HYP*

Hemophilia A

ALPROLIX*

ELOCTATE*

Hemophilia B

PLEGRIDY

Secondary Progressive Multiple SclerosisTYSABRI

Neublastin

Anti-TWEAK

Anti-LINGO

BG00011

ISIS-SMNRx*

BIIB037*

TYSABRI

Multiple SclerosisBIIB061

E2609*

Alzheimer's DiseaseBAN2401*

FDA APPROVED

FDA APPROVED

Lat

e-S

tag

eE

arly

-Sta

ge

* Partnered program

ISIS-DMPKRx* Myotonic Dystrophy

Systematic Lupus Erthematosus

www.biogen.com*Status as of May 2015

Anti-CD40 Ligand (CDP7657)

FDA APPROVED

Multiple SclerosisAnti-LINGO

Acute Optic Neuritis

http://www.biogen.com/



Daclizumab HYP*

Multiple Sclerosis

*Daclizumab HYP is an investigational candidate



Daclizumab HYP• Daclizumab HYP is a humanized monoclonal antibody that binds to CD25, the alpha

subunit of the high affinity IL-2 receptor that is expressed at high level on the T-cells

thought to become abnormally activated in autoimmune conditions, such as MS1

IL-2 signaling is maintained via the intermediate - affinity IL-2 receptor in the presence of daclizumab

Figure: Sheridan JP, et. al. (Poster P430) Presented at the 25th Congress of European Committee for Treatment and Research in Multiple Sclerosis; Düsseldorf, Germany, September 9-12, 20091. Rose JW et al. Amer Acad Neurology. 2007: 69;785-7890

High-affinity IL-2 receptor Intermediate affinity IL-2 receptor



γγ

The IL-2 Receptor

IL-2Rα(CD25)

IL-2Rβ(CD122)

γC(CD132)

αIL-2

β

IL-2

β

High-affinityIL-2R

Intermediate-affinityIL-2R

DAC HYP=daclizumab high-yield process; IL=interleukin; R=receptor; γC=common gamma chain1. Wiendl H, Gross CC. Nat Rev Neurol. 2013;9:394-40.

IL-2Rβ(CD122)

γC(CD132)

The high-affinity IL-2R is composed of IL-2Rα, IL-2Rβ, and γC

R IL-2Rα (CD25) has no known signaling function

R IL-2Rβ and γC harbor all signaling capability

The intermediate-affinity IL-2R is composed of IL-2Rβ and γC but lacks the IL-2Rα1



Daclizumab HYP Proposed Mechanism of Action

IL-2Rα(CD25)

IL-2Rβ(CD122)

γC(CD132)

α

βγ

High-affinityIL-2R

DAC HYP=daclizumbab high-yield process; IL=interleukin; R=receptor; γC=γcommon. Wiendl H, Gross CC. Nat Rev Neurol. 2013;9:394-40.

βγ

Intermediate-affinityIL-2R

IL-2Rβ(CD122)

γC(CD132)

DAC HYP binds the subunit (CD25) of the high-affinity IL-2R and blocks its interaction with IL-2

DAC HYP does not block interaction between IL-2 and intermediate-affinity IL-2R



Daclizumab HYPOverview of Development1

2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016

CHOICE (phase 2)DAC* add-on with IFNβ

SELECT (phase 2)DAC HYP vs placebo

SELECTION (phase 2)

DAC HYP blinded extension of SELECT

SELECTED (phase 2)DAC HYP open-label extension of SELECTION

DECIDE (phase 3)DAC HYP vs IM IFNβ-1a

EXTEND (phase 3)DAC HYP open-label extension of DECIDE

N=621

N=420

N=517

N=1841

N=1204

N=230

*CHOICE used an investigational form of aclizumab different from daclizumab HYP1Status as of May 2015

DAC=daclizumab; HYP=high-yield process; IFN=interferon; IM=intramuscular; RRMS=relapsing-remitting multiple sclerosis.



SELECT: MRI Substudy Design OverviewSELECT: MRI Substudy Design OverviewSELECT: Design Overview

52-Week Treatment Period

DAC HYP 300 mg SC every q4w

DAC HYP 150 mg SC q4w

Placebo

Primary endpoint

• Annualized RelapseRate

Secondary endpoints

• New Gd+ lesions at weeks 8–24(MRI substudy n=307)

Tertiary endpoint

• EDSS disability progression at week 52• New T2 lesions at week 52

• Proportion of subjects relapsing

• Change in MSIS-29 physical score (quality of life measure)

0 4 8 12 16 20 24 28 32 36 40 44 48 52

Randomization307 patients

Randomizationn=621 patients

Gold R, et al; SELECT study investigators. Lancet. 2013;381:2167-75.



Series10

0.1

0.2

0.3

0.4

0.5

0.46

0.21 0.23

Ad

juste

d A

RR

SELECT Results: Annualized Relapse Rate (Primary Endpoint)

Placebo (n=196)

DAC HYP 150 mg (n=201)


ARR=annualized relapse rate; DAC HYP=daclizumab high-yield process; EDSS=Expanded Disability Status Scale. Gold R, et al; SELECT study investigators. Lancet. 2013;381:2167-75.

*Estimated from a negative binomial regression model adjusted for number of relapses in 1-year period before trial entry, baseline EDSS score (≤2.5 vs >2.5), and age (≤35 vs >35 years)

Adjusted ARR at end of trial (week 52)

54%relative

reduction vs placeboP<0.0001*

50%relative

reduction vs placeboP=0.0002*



*Estimated from a proportional odds model adjusted for the baseline number of Gd+ lesions

SELECT Results: MRI Outcomes

Placebo (n=195)



DAC HYP=daclizumab high-yield process; Gd+=gadolinium-enhancing.Gold R, et al; SELECT study investigators. Lancet. 2013;381:2167-75.

Mean number of new Gd+ lesions at week 52

Placebo (n=195)


DAC HYP

300 mg (n=200)*Estimated from a negative binomial regression model

adjusted for the baseline number of T2 lesions

Adjusted mean number of new/newly enlarging T2 lesions at week 52

Series10

0.25

0.5

0.75

1

1.25

1.5

1.4

0.3 0.2

Me

an

no

. of

Gd

+ le

sio

ns

79% relative

reduction vs placebo P<0.0001*

86% relative


Series10

1

2

3

4

5

6

7

8

9

8.1

2.4 1.7A

dju

ste

d m

ea

n n

o.

of

T2

les

ion

s

70% relative


79% relative




Confirmed Disability Progression at End of SELECT

Placebo DAC HYP 150mg DAC HYP 300mg

Proportion with 3-month confirmed disability progression

13.3% 5.9% 7.8%

*Estimated from Cox-proportional hazards model adjusting for baseline EDSS (≤2.5 vs. >2.5), and age (≤35 vs. >35), Gold R, et al; SELECT study investigators. Lancet. 2013;381:2167-75

0.00

0.05

0.10

0.15

0 12 24 36 48 52Time on study (weeks)

Pro

po

rtio

n o

f p

atie

nts

wit

h 1

2-w

eek

con

firm

ed d

isab

ility

pro

gre

ssio

n

43%ReductionP=0.091*

57%ReductionP=0.021*

DAC HYP 150mg DAC HYP 300mg

Placebo

.



SELECT: Adverse Events That Occurred in >5% of Patients During the Treatment Period

AEPlacebo(n=204)


DAC HYP 300 mg(n=209)

MS relapse 38% 23% 20%

Nasopharyngitis 15% 14% 14%

Upper respiratorytract infection

7% 9% 11%

Headache 10% 10% 10%

Pharyngitis 3% 6% 5%

Gold R, et al; SELECT study investigators. Lancet. 2013;381:2167-75.



SELECT: Adverse Events of Interest

AEPlacebo(n=204)



Infections 44% 50% 54%

Serious infections 0% 3% 1%

Cutaneous events* 13% 18% 22%

Injection site reaction, erythema, induration

1% 2% 2%

Serious cutaneous events 0% <1% 1%

Malignancy <1% <1% <1%

Death† 0 1 (<1%) 0

*Cutaneous events are those treatment-emergent AEs whose preferred term contains the word dermatitis, rash, or erythema, or whose preferred term is one of the following: drug eruption, drug hypersensitivity, dyshidrosis, eczema, granuloma annulare, pityriasis rosea, psoriasis, skin exfoliation,toxic skin eruption, urticaria. †Patient recovering from serious cutaneous event died due to a complication of psoas abscess and ischemic colitisGold R, et al; SELECT study investigators. Lancet. 2013;381:2167-75.



Abnormalities of ALT/AST >5× ULN•Typically occurred late in the treatment period (median onset day = 308)

•Median recovery time = 62 days

– 7 patients resumed or continued therapy. None of these patients had a recurrence in the liver function test or abnormality in the next 5 months (the minimum period for which follow-up was available)

SELECT: Incidence of ALT/AST Abnormalities

ALT/ASTPlacebon=204

DAC HYP150 mgn=208

DAC HYP300 mg n=209

1–3× ULN, n (%) 64 (31) 54 (26) 62 (30)

3–5× ULN, n (%) 6 (3) 7 (3) 6 (3)

>5× ULN, n (%) 1 (<1) 9 (4) 8 (4)

ALT=alanine aminotransferase; AST=aspartate aminotransferase; ULN=upper limit of normal.Gold R, et al; SELECT study investigators. Lancet. 2013;381:2167-75







24-week washout (n=86)

24-week washout (n=88)

DAC HYP 150 mg

DAC HYP 300 mg

SELECTION: N=517

0 4 8 12 16 20 24 28 32 36 40 44 48 52

Primary endpoint

• Safety and immunogenicity

SELECT and SELECTION: Design Overview

Gold R et al. Lancet. 2013;381:2167-2175; Giovannoni G et al. Lancet Neurol. 2014;13:472-481.

Primary endpoint

• Annualised relapse rate

DAC HYP 300 mg SC every 4 weeks (n=209)

DAC HYP 150 mg SC every 4 weeks (n=208)

Placebo (n=204)

0 4 8 12 16 20 24 28 32 36 40 44 48 52

SELECT: N=621

Double-Blind Treatment



SELECTION: Annualized Relapse Rate

DAC HYP results are combined data for patients on continuous treatment with 150 mg or 300 mg.Giovannoni G et al. Lancet Neurol. 2014;13:472-481.

Series10.00

0.10

0.20

0.30

0.40

0.50

0.43

0.150.17

An

nu

aliz

ed R

elap

se R

ate

Year 1Placebo (n=163)

Year 1DAC HYP(n=129)




0.0

0.1

0.2

0.3

DAC HYP continuous

0 12 2463 9 15 18 21

DAC HYP

Placebo

Placebo

16%

12%

DAC HYP

DAC HYP after placebo

6%

13%

Placebo patients startDAC HYP

Time on study (months)

Pro

po

rtio

n o

f p

atie

nts

wit

h c

on

firm

ed d

isab

ilit

y p

rog

ress

ion

SELECTION: Confirmed Disability Progression over 2 Years of DAC HYP Treatment

Placebo patients start DAC HYP

Placebo

DAC HYP

DAC HYP

Placebo year 1

DAC HYP year 1

DAC HYP continuous

DAC HYP after placebo

16%

13%

7% DAC HYP(Year 2)n=163

0 3 6 9 12 15 18 21 24Time on Study (months)

Pro

po

rtio

n o

f P

atie

nts

wit

h 3

-Mo

nth

Co

nfi

rmed

Dis

ab

ilit

y P

rog

ress

ion

0.3

0.2

0.1

0.0


12%

DAC HYP



SELECTION: MRI Assessments After 2 Years

New or Newly Enlarging T2 Lesions


Series10.0

1.0

2.0

3.0

4.0

5.0

6.0

7.0

8.0

9.0

10.0

8.0

1.91.2M

ean

Nu

mb

er o

f N

ew/E

nla

rgin

g

T2-

Hyp

erin

ten

se L

esio

ns

Year 1Placebo (n=163)





SELECTION: After 24-Week Washout from DAC HYP, Gd+ Lesions were Below Pre-treatment Baseline

1.9

1.2

0.5

0.2

0.4

0.2

1.2

0.9

0.2 0.2

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

1.8

2 SELECT BaselineWk 24Wk 52Wk 72 (End of 24-wk washout)Wk 104 (32-wks after restarting therapy)

DAC HYP 300 mgDAC HYP 150 mg

End of 24 week washout

End of 24 week washout

Nu

mb

er

Ne

w G

d+

Le

sio

ns

(m

ea

n)

Year 1 Year 2 Year 1 Year 2DAC HYP results are combined data for patients on continuous treatment with 150 mg or 300 mg.Giovannoni G et al. Lancet Neurol. 2014;13:472-481.



SELECTION: Adverse Events of Interest







Serious Infections, n (%) 3 (3) 1 (1) 2 (2) 2 (2) 3 (3) 2 (2)

Serious Cutaneous Events, n (%)

2 (2) 0 0 3 (3) 1 (1) 0

ALT/AST > 5x ULN, n (%) 1 (1) 1 (1) 0 3 (3) 2 (2) 4 (5)

Malignancy, n 0 1 (1) 0 0 0 0

Death* 0 0 0 0 0 1 (1)

DAC HYP StartersYear 1 of DAC HYP

DAC HYP ContinuousYear 2 of DAC HYP

DAC HYP Washout / Reinitiation

ALT, alanine aminotransferase; AST, aspartate aminotransferase; ULN, upper limit of normal


*One patient in the washout and re-initiation group died because of autoimmune hepatitis after re-initiation of 300 mg daclizumab HYP



DECIDE: Study Design Overview

All subjects had a minimum of 2-years and maximum of 3-years of treatment

Trial ended when last subject randomized completed 2-years

96-144 week treatment period

Randomization(n=1841)

CD56bright NK cell count* CD56

0 4 8 12 16 20 24 28 32 36 40 44 48 96-144CD56

CD56

CD56

CD56

CD56

CD56

CD56

IM IFNβ-1a 30 μg every 1 week (n=922)

SC DAC HYP 150 mg every 4 weeks (n=919)

Follow-up

Brain MRI

EDSS EDSS and MSFC-3 assessments*

EDSS EDSS EDSS EDSS EDSS EDSS

* Also assessed at weeks 60, 72, 84, 108, 120, 132, 144EDSS, Expanded Disability Status Scale; DAC HYP=daclizumab high-yield process; IFN=interferon; IM=intramuscular; MSFC-3=Multiple Sclerosis Functional Composite; NK=natural killer; SC=subcutaneous; Kappos L, Selmaj K, Arnold D, et al. Primary results of DECIDE: a randomized, double-blind, double-dummy, active-controlled trial of daclizumab HYP vs. interferon β-1a in RRMS patients. Presented at: Joint ACTRIMS-ECTRIMS Meeting. September 10-13, 2014. Boston, MA

24-week follow-up



DECIDE: Primary Endpoint Annualized Relapse Rate

Kappos L, Selmaj K, Arnold D, et al. Primary results of DECIDE: a randomized, double-blind, double-dummy, active-controlled trial of daclizumab HYP vs. interferon β-1a in RRMS patients. Presented at: Joint ACTRIMS-ECTRIMS Meeting. September 10-13, 2014. Boston, MA

IFN beta-1a 30 mcg (n=922) DAC HYP 150 mg (n=919)0

0.05

0.1

0.15

0.2

0.25

0.3

0.35

0.4

0.45

0.393

0.216

45% Reduction (95% CI: 35.5%, 53.1%) p<0.0001

AR

R



DECIDE: MRI Results


Series10123456789

10Chart Title

9.4

4.3

*New/Newly Enlarging T2 Lesions54% Reduction

P<0.0001

Series10

0.2

0.4

0.6

0.8

1

1.2Chart Title

1.0

0.4

†New Gd+ Lesions65% Reduction

P<0.0001

Series10

0.51

1.52

2.53

3.54

4.55

Chart Title

4.4

2.1

†New T1 Hypointense Lesions‘blackholes’

52% ReductionP<0.0001

Mea

n nu

mbe

r of

lesi

ons

IFN beta-1a 30 mcg DAC HYP 150 mg

n=841 n=864 n=909 n=900 n=908 n=899

*2-year endpoint† Tertiary Endpoints



DECIDE: Results Confirmed Disability Progression


*3-month confirmed: Patients censored after tentative progression (n-67) analyzed per primary method in the statistical analysis plan; secondary endpoint; all imputed as non-progressors;†6-month confirmed: Patients censored after tentative progression (n=108) imputed per observed rate in trial; tertiary endpoint. Estimated proportions are the average over imputed datasets. For both endpoints risk reduction based on Cox proportional hazards model adjusted for baseline EDSS, history of prior IFN use, and age.



DECIDE: Overview of Safety

* All deaths were considered unrelated to treatment. The death in the DAC HYP group was due to aspiration pneumonia in a patient who had a MS relapse involving the brain stem and after withdrawing from the study. Deaths in the IFN beta-1a group were due to myocardial infarction, completed suicide, metastatic pancreatic cancer and peritonitis. AE, adverse event; SAE, serious adverse event


DECIDE: Overview of Safety



DECIDE: Common Adverse Events≥10% of patients in any treatment group

Selmaj K, et al. Safety and tolerability of daclizumab HYP treatment in relapsing-remitting multiple scleorosis: Results of the DECIDE study. Presented at: Joint ACTRIMS-ECTRIMS Meeting. September 10-13, 2014. Boston, MA



DECIDE: Adverse Events of Interest

*Clinical assessment of causality based on structured approach (Rockey et al. 2010. Hepatology 51:2117). One case in each group with

causality score of “probable” or higher. ALT, alanine aminotransaminase; AST, aspartate aminotransaminase; ULN, upper limit of normal.




Anti-LINGO-1*

Multiple Sclerosis (MS) & Acute Optic Neuritis (AON)

*Anti-LINGO is an investigational candidate



Anti-LINGO-1

• Multiple Sclerosis (MS) and Acute Optic Neuritis (AON)

• Current treatments focus on targeting the immunological response

• Anti-LINGO-1 (BIIB033) is the first drug candidate that targets CNS

repair in MS through remyelination1

• LINGO-1 is a CNS-specific, leucine-rich repeat (LRR) and lg-domain,

membrane-associated glycoprotein2

• Hypothesized that blocking the action of LINGO-1 may allow neuronal

repair and remyelination following CNS injury1

Data on File. Biogen.1. Rudick R et al. Expert Opin. Biol. Ther. 2008; 8(10):1561-15702. Mi S, et al. Nature. 2004: 7; 221-228



Anti-LINGO-1

Ndubaku U, deBellard ME. Acta Histochem. 2008;100:182-195.

Immature oligodentrocytes

Mature oligodendrocyte

Adapted from Jackman N et al. Physiology. 2009;24:290-297; Zhang SC. Nat Rev Neurosci. 2001;2:840-843.

Myelinatingoligodentrocytes

Lingo-1 protein prevents oligodendrocyte maturation

LINGO-1, allrly

LINGO-1, allrly

LINGO-1, allrly

Anti-LINGO-1 antibody binds LINGO-1, allowing oligodendrocytes to mature and function properly



Co

ntr

ol

RN

Ai

LIN

GO

-1 R

NA

i

P<0.001

No RNAi

Control RNAi

LINGO-1RNAi

0

5

10

15

20

25

Mat

ure

Olig

od

end

rocy

tes

(%

To

tal)

LINGO-1 Blockade Resulted in Oligodendrocyte Differentiation

RNAi=ribonucleic acid interference. Mi S et al. Nat Neurosci. 2005;8:745-751.



Cuprizone model(1 µg/local)

Lysolecithin model(1 mg/kg/IP)

Experimentalautoimmuneencephalitis (EAE)(3 mg/kg/IP)

Anti-LINGO-1 Antibody Resulted in Remyelination in Animal Models of Demyelination

*

* *

**

Adapted from Mi S et al. Ann Neurol. 2009;65:304-315; Mi S et al. Presented at ECTRIMS; October 13–16, 2010; Gothenburg, Sweden. P731.

*

**

*

Control Anti-LINGO-1

*Demyelinated Axons Remyelinated Axons

*


20

40

60

80

Mye

lin

ated

Axo

ns

(%)

*P<0.05


20

40

60

80

Mye

lin

ated

Axo

ns

(%) *P<0.02


20

40

60

80

Mye

lin

ated

Axo

ns

(%)

*P<0.05



Anti-LINGO-1 Phase 1 Studies: Safety in Humans

*90% effective concentration.SC=subcutaneous; RRMS=relapsing-remitting MS; SPMS=secondary progressive MS; PK=pharmacokinetics; T1/2=half life.Tran J et al, Neurology Neuroimmunology (N2 Journal) 2014; 1 (18)

Completed Single Ascending Dose (IV And SC) Study in Healthy Volunteers and a Multiple Ascending Dose (2 IV Doses 2 Weeks Apart)

in MS Subjects (RRMS and SPMS)

• In the multiple ascending dose study, common adverse events for anti-LINGO-1 at doses ranging from 0.3 mg/kg–100 mg/kg (combined) vs placebo were

– Urinary tract infection (16% vs 13%)

– Headache (16% vs 13%)

– Upper respiratory tract infection(9% vs 20%)

• PK was linear with a T1/2 typical of a mAb (≈2–3 weeks)

• CSF penetration was low (≈0.1% of serum levels), but concentrations reached levels ≥EC90* values at 10 mg/kg dose

• Findings supported advancing into phase 2 studies



Anti-LINGO-1 Phase 2 Studies

IM=intramuscular; IFNβ=interferon beta; EDSS=Expanded Disability Status Scale; T25FW=Timed 25-Foot Walking Test; 9HPT=9-Hole Peg Test; PASAT=Paced Auditory Serial Addition Test; DTI=diffusion tensor imaging.Cadavid D et al. Presented at AAN; April 26–May 3, 2014; Philadelphia, PA USA. RENEW: P2.262; SYNERGY: P3.154.

RENEWAcute Optic Neuritis

• Placebo-controlled proof of biology

• Subjects with recent first episode of acute optic neuritis

• Dose: 100 mg/kg q4wks×6

• Endpoints:

– Visual evoked potential (VEP)/multifocal VEP (latency delay)

– Optical coherence tomography (retinal nerve fiber and ganglion cell layer loss)

– Visual function (low contrast letter acuity, visual quality of life)

SYNERGYRelapsing Forms of MS

• Placebo-controlled proof of concept and dose ranging

• Subjects with RRMS and relapsing SPMS receiving IM IFNβ-1a

• Dose: 3, 10, 30, 100 mg/kg q4wks×18

• Physical and cognitive endpoints:

– EDSS/T25FW/9HPT/PASAT composite

– Primary=improvement

– Key secondary=delayed progression

– MS-COG (information processing and learning and memory)

– MRI (MTR, DTI, black holes, atrophy)



Anti-LINGO-1 Phase 2 AON Study (RENEW)Completed

• Subjects with first episode of acute optic neuritis

• N=82 subjects randomized, 2 arms, 33 sites

• Evaluating efficacy after onset of inflammatory CNS demyelination in a clinically

eloquent area (the optic nerve)

–The visual system affords an opportunity to study the functional consequences of CNS remyelination

»Neurophysiology (VEP/mfVEP)»Survival of retinal ganglion cells (OCT)»Clinical benefit (contrast acuity)

• Top line results revealed evidence of proof of biology for remyelination

• 34% improvement in average FF-VEP latency recovery at 24wks (p-0.0504)

VEP=visual evoked potential; mfVEP=multifocal VEP; OCT=optical coherence tomography.



Anti-LINGO-1 Phase 2 MS Study (SYNERGY)Fully-enrolled and ongoing*

• Active relapsing forms of MS

• 418 patients enrolled, 5 arms, 72 sites, 12 countries

• Active relapsing MS patients will receive IM IFN beta-1a plus anti-LINGO-1

(4 doses) or IM IFN beta-1a plus placebo

• 18-months treatment duration allows study of clinical benefit

• Allows the study of efficacy in preventive mode (with drug on board before

new lesions develop) but also on pre-existing lesions

• Advanced MRI methodology to study the morphological features of CNS

repair

*As of May 2015



TYSABRI® (natalizumab)*

Secondary Progressive MS (SPMS)

*Though approved for some indications, TYSABRI is an investigational candidate for SPMS



Secondary Progressive MS (SPMS)• Prevalence

»Majority of patients with relapse remitting multiple sclerosis (RRMS) eventually develop secondary progressive multiple sclerosis (SPMS)»50% at 10 years; 90% at 25 years»At any given time, 30-40% of MS patients suffer from progressive disease1

• SPMS Pathology

»Intrathecal chronic inflammation drives secondary neurodegeneration via soluble toxic mediators in the CSF2 »41% of brain autopsy specimens have ectopic meningeal lymphoid tissues3

1. Protocol 101MS326 Biogen Idec. 2. UK MS Brain Tissue Bank Data. 3. Magliozzi R et al, 2007.



Natural History of MS:Clinical and MRI Measures

Time

Relapsing-Remitting MS

Secondary Progressive MS

Preclinical

MRI ActivityBrain Volume

Relapses/Disability

Dis

abili

ty

MRI T2 lesion load

Data on File. Biogen



RRMS SPMS: Moving from an Acute, Focal Inflammatory Process to Chronic, Compartmentalized Global Inflammation

RRMS Exacerbation

Major InflammationVery high chemokine levels

Early Progressive MS

Less InflammationModerate-low chemokine

levels

CIS, RRMS

InflammationModerate chemokine levels

Late Progressive MS

Low, but significant chemokine levels

Acute Gd+ Lesions(White Matter)

Meningeal Foci(Grey Matter)

“Chronic lesions”

Cortical Pathology

Illustration by Diego Cadavid and Jeff Browning. Biogen

Meningeal lymphoid germinal-like centers

Perivascular white matter

infiltrates

Modified from Uccelli et al. 2005. Trends Immunol. 26:254-259



Clinical Features of Progressive MS Phenotypes

MS, multiple sclerosis; PPMS, primary progressive MS; SPMS, secondary progressive MS.1. Miller DM, Leary SM. Lancet Neurol. 2007;6:903-912; 2. Tremlett H et al. J Neurol. 2009;256:374-381; 3. Harding KE et al. J Neurol Neurosurg Psychiatry. 2014;Jun 4. [Epub ahead of print]; 4. Holper L et al. J Neurol. 2010;257:103-113; 5. Thompson AJ et al. Brain. 1997;120:1085-1096; 6. Comi G. Mult Scler. 2013;19:1428-1436; 7. Comi G et al. J Neurol Sci. 1995;132:222-227.

Motor impairment

• Progressive spastic paraparesis (weakness in the legs)1

»Presenting symptom in majority of patients with progressive forms of MS (80%)»Involves impaired mobility with weakness, stiffness, clumsiness, dragging of legs»Impacts ability to walk long distances without rest

• Progressive ataxic syndrome with cerebellar and brainstem involvement

»Second most common presentation (15%)1-3

• Upper limb dysfunction and impairment in activities that require manual dexterity4

Bladder and bowel dysfunction

• Urgency and incontinence1

• Predominant spinal cord involvement5,6

Cognitive symptoms

• Progressive cognitive deficits are infrequent

• Less common in PPMS than SPMS7



Rationale for Natalizumab Treatment in SPMS

1. Christensen JR et al. Neurology. 2014;82;1499-1507.

2. Sellebjerg et al. Multiple Sclerosis. 2012.18(S4):514-515.

It is believed to prevent trafficking of lymphocytes across blood vessels and into the brain and spinal cord

May also suppress inflammation within the CNS1

• Possible reduction in CXCL13 levels in the CSF of patients with active and progressive MS

• Possible reduction in intrethecal levels of osteopontin, another molecule that has been implicated in MS progression at the experimental level

Post-hoc analyses of relapsing and non-relapsing SPMS studies suggest that natalizumab may be beneficial (T25FW, 9HPT)2



Ongoing Development & Research

ASCEND Trial Overview

»An investigation of whether TYSABRI treatment slows the accumulation of disability not related to relapses in patients with SPMS

»Primary endpoint: the proportion of subjects experiencing confirmed progression of disability as measured by a composite endpoint

»FDA special protocol assessment (SPA) obtained with accepted regulatory endpoint

»Study fully enrolled in May 2013 (N=889)

»Data readout expected 2015

Data on File. Biogen. SCR=screening; R=randomization; IV=intravenous; q4w=once every 4 weeks.



TYSABRI® (natalizumab)*

Acute Ischemic Stroke

*Though approved for some indications, TYSABRI is an investigational candidate for acute ischemic stroke



TYSABRI in Ischemic Stroke

Prevalence

–There are nearly 800,000 strokes of all types per year in the US

–Ischemic stroke accounts for approximately 80%

Treatment

–Recombinant tissue plasminogen activator (rtPA) only approved pharmacological therapy for acute ischemic stroke. Must be used within 3 hours of stroke onset (US Guidelines)

–TYSABRI could be used as an adjunctive therapy with TPA

–Blocking the α4β1 integrin with natalizumab is expected to reduce peri-stroke inflammation and thereby reduce the expansion of the infarct due to inflammation

–Potential to be the first disease-modifying, anti-inflammatory therapeutic for stroke, with better efficacy and safety than TPA

–As a result of acute dosing, PML is not expected to be an observed AE in stroke.

Data On File. Biogen.Roger 2011 (From Protocol 101SK201)



Clot within artery blocks normal flow to the brain

Loss of blood supply results in ischemia

Two major zones of injury: ● Core ischemic zone

● Ischemic penumbra

Saver JL. Stroke 2006;37:263–6

Blockage Ischemic tissue Ischemic Penumbra Core ischemic zone

Etiology of Acute Ischemic Stroke (AIS)Obstructed blood flow in the brain leads to ischemia

Ischemia = restriction in blood supply to tissues Core ischemic zone = area of severe ischemia (blood flow <10–25%)Ischemic penumbra = rim of mildly-to-moderately ischemic tissue

Infarction

Penumbra

Thrombus



Golden treatment window during which pharmacologic or mechanical

interventions are most likely to be effective

Etiology of Acute Ischemic Stroke (AIS) Ischemia leads to infarction (neuronal death)

1. The Internet Stroke Center. The Ischemic Penumbra. Available at: www.strokecenter.org. Accessed: Jan 2014; 2. Saunders DE et al. Stroke 1995;26:2272–6

Minutes after blockage, an ischemic cascade is initiated, leading to neuronal death (infarct) at the core zone

Unless blood flow is promptly restored, the penumbra also infarcts, resulting in a larger total infarct volume1

The larger the infarct volume, the worse the clinical outcomes for AIS patients2



Acute and long-term functional outcomes in AIS Type and degree of long-term disability depend upon area of brain affected and extent of damage

*p=0.001. AIS=acute ischemic stroke; mRS=modified Rankin ScalePetty GW et al. Stroke 2000;31:1062–8

Before stroke Maximal deficit 90 days after stroke 1 year after stroke0

102030405060708090

100

75.6

27.4

53.7 50.3

9.8

43.935.8

41.6

Functional status (mRS) among AIS patients

No significant or slight disability

Moderately severe or severe disability

Pat

ien

ts (

%)

Common long term outcomes

paralysis/problems controlling movement problems using or understanding language

sensory disturbances problems with thinking and memory

emotional disturbances

No significant or slight disability: Rankin score of I or II; Moderately severe or severe disability: Rankin score of IV, V or dead



Natalizumab as AIS TherapyNatalizumab is believed to block the migration of lymphocytes that are thought to mediate post-AIS inflammatory responses that increase infarct volume

α4β1integrin

VCAM-1

1. Natalizumab, an a α4β1 integrin antibody ( ), binds to α4β1 integrin receptors on all human leukocytes (except polymorphonuclear leukocytes)1

2. Natalizumab binding blocks CNS α4β1 integrin from interacting with its ligand, vascular cell adhesion molecule-1 (VCAM-1), on the endothelial wall1

3. Blocking entry of leukocytes into the brain suppresses the inflammatory activity thought to cause post-AIS increases in infarct volume2

CNS=central nervous system, 1. Rudick RA et al. NEJM 2006;354:911–23; 2. Protocol 101SK201. Data on file. Biogen, Jun 2013



Primary objective: To assess the effect of natalizumab on infarct volume over first 5 days after stroke

Secondary objectives – to assess: The effect of natalizumab on infarct growth

at multiple time points after ischemic stroke The effect of natalizumab on disability and

neurological function (BI, mRS, NIHSS etc) The safety of natalizumab via physical and

neurological examinations: o vital sign measurements o hematology and blood chemistry o anti-natalizumab antibodies o monitoring of AEs and SAEs

ACTION Phase II StudyEffect of a single dose of natalizumab infarct volume in AIS patients who have either already received, or are ineligible for, IV rt-PA treatment

AIS=acute ischemic stroke; AE=adverse event; BI=Barthel index; mRS=modified Rankin Scale; NIHSS=National Institute of Health Stroke Scale; SAE=serious adverse eventProtocol 101SK201. Data on file. Biogen, Jun 2013; Clinicaltrials.gov NCT0195570, accessed April 25 2014

Baseline

Day 5

5 days



Anti-TWEAK (BIIB023)*

Lupus Nephritis

*Anti-TWEAK is an investigational candidate. Efficacy and safety have not been established.



Lupus Nephritis

Prevalence

–Lupus Nephritis (LN) is present in up to 60% of Systemic Lupus Erythematosus (SLE) patients.1 (SLE occurs in approximately 20 to 70 cases per 100,000)2

Treatment

–No indicated therapies

–Treatment regimens include combination Mycophenolate mofetil with prednisone or cyclophosphamide with methypredinisolone

–Suppress the immune system to treat the acute inflammatory injury3

–Limited efficacy with increasing toxicities over time4

1. Cameron J. J of Amer Society of Nephrology. 1999; 10(2):413-4242. Pons-Estel GJ et al. Seminars in Arthritis and Rheumatism. 2010; 39(4): 257-2683. Ortega L et al. Lupus. 2010; 19:557-5744. Waldman M and Appel GB. Kidney International. 2006; 70:1403-1412



Anti-TWEAK (BIIB023)

• TWEAK is a proinflammatory cytokine

expressed by WBCs and functions as a

soluble cytokine through the fibroblast growth

factor (FGF)-inducible molecule 14 (Fn14)

• Fn14 is highly induced in disease target

tissues and implicated in the pathogenesis of

LN

• Anti-TWEAK is thought to target Fn14 and is

designed to inhibit glomerular and tubular

pathologies1

• Phase II study ongoing and expected to be

completed in 20192

1. Sanz AB et al. Kidney International. 2011; 80:708-7182. www.clinicaltrials.gov NCT01930890Data on File. Biogen.



BIIB023 Study Design

Protocol 211LE201 Data on File. Biogen



Neublastin (BG00010)*

Neuropathic Pain

*Neublastin is an investigational candidate. Efficacy and safety have not been established.



Neuropathic PainPrevalence

–Estimated 1-2% of population experiences neuropathic pain. Possibly underestimated due to undiagnosed chronic pain1

–Associated with physical injury to a nerve, systemic diseases (e.g. diabetes), autoimmune disorders, infections, etc.2

Treatment

–Current therapies: LYRICA® (pregabalin), NEURONTIN® (gabapentin), CYMBALTA® (duloxetine)

»Poor control of pain with increased side effects3

1. Smith BH and Torrance N. Curr Pain Headache Rep. 2012.2. NINDS.NIH.gov 04-48533. Investigator Brochure V7; Biogen.

LYRICA® and NEURONTIN® are a registered trademarks of Pfizer Inc.; CYMBALTA® is a registered trademark of Eli Lilly and Company



Neublastin (NBN)

• NBN is a potent cell survival and growth factor which

signals through receptor GFRα3 highly expressed on

pain-sensing neurons1

• Possible targeted alleviation of pain and minimal CNS

side effects were shown in animal studies

• NBN is being investigated as a first-in-class,

potentially restorative treatment for neuropathic pain

and neuropathy associated with nerve damage2

• Phase 2 study expected to be completed 20153

1. Gardell L et al. Nature. 2003; 9:1383-13892. Data on File. Biogen.3. www.clinicaltrials.gov NCT01873404



Neublastin – Program DevelopmentPhase 1 SAD and MAD studies complete

Phase 2 POC Study in lumbar radiculopathy on-going

–Multi-center, double-blinded, placebo‑controlled study, multi-dose study (~ 168 patients)

–Neublastin (50, 150, 400, 800, and 1200 µg/kg) vs placebo IV three times a week for approximately 13 weeks

–Primary endpoint: Change from baseline in the mean 24-h average general pain intensity score (AGPI) at the end of the treatment week using an 11‑point Numeric Rating Scale (NRS)

Protocol 103NS201 v6



ISIS-SMNRX*

Spinal Muscular Atrophy

*ISIS-SMNRX is an investigational candidate. Efficacy and safety have not been established.



Spinal Muscular Atrophy (SMA)

SMA is an autosomal recessive neuromuscular disease. It results in the degeneration of alpha

motor neurons in the spinal cord leading to proximal muscle weakness and paralysis.

– Prevalence

»Approximate incidence is 1 in 6,000 to 1 in 10,000 live births1

– Though classified into three major types, the disorder demonstrates a continuous range of severity and overlap2

1. D’Amico A et al. Orphanet Journal of Rare Diseases. 2011; 6 (71); http://www.ojrd.com/content/6/1/712. Mitchell LR et al, Lancet. 2008; 2120-2133; http://www.ncbi.nlm.nih.gov/books/NBK1352/

Type Other Names Age at Onset Life SpanHighest Function

Achieved

SMA IAcute spinal muscular

atrophy; Werdnig Hoffmann disease

0-6 months <2 years Never sit independently

SMA IIChronic spinal muscular

atrophy; Dubowitz disease7-18 months

Varies from 2 years to the third decade of life

Sit independently, never stand

SMA IIIJuvenile spinal muscular

atrophy; Kugelberg-Welander disease

>18 months Normal Stand and walk alone



Spinal Muscular Atrophy (SMA)

SMA caused by genetic defects in the SMN1 gene that result in the lack of functional SMN protein» Intervention: Antisense oligonucleotide (ASO) to insert missing exon in “backup”

gene

ISIS-SMNRX is believed to increase production of fully functional SMN protein in model systems

Uniformly 2’-0-methoxyethyl modified (MOE) antisense drug1

Current Treatments:

» No indicated therapies for SMA. Treatment centers around the management of symptoms and preventing complications of SMA

1. Chiriboga, C et al. Results of an Open-Label, Escalating Dose Study to Assess the Safety, Tolerability, and Dose Range Finding of a Single Intrathecal Dose of ISIS-SMN RX in Patients with Spinal Muscular Atrophy. Presented at AAN 2013



ISIS-SMNRX

• ISIS-SMNRX is currently in Phase 3 trials;

estimated to be completed in 20172

• Granted Orphan Drug Status in US & EU

and Fast Track in the US1

• ISIS-SMNRX is a joint collaboration with

ISIS Pharmaceuticals

1. Darras, B et al. Interim Results of a Phase 2 Study of ISIS-SMNRx in Children with Spinal Muscular Atrophy. Presented at AAN 20142. www.clinicaltrial.gov NCT02193074Data on File. Biogen.



Phase 2 Multiple-Ascending Dose, Open-Label Study in Medically Stable SMA Patients 2-15 Years of AgeStudy Complete

Objectives

Evaluate the safety and tolerability of multiple intrathecal doses of ISIS-SMNRx

Evaluate CSF, plasma PK, and clinical outcomes related to SMA (including HMFSE)

Darras, B et al. Interim Results of a Phase 2 Study of ISIS-SMNRx in Children with Spinal Muscular Atrophy. Presented at AAN 2014



Dose and Time Dependent Increases in HFMSE Scores after Multiple Doses of ISIS-SMNR*

Darras, B et al. Interim Results of a Phase 2 Study of ISIS-SMNRx in Children with Spinal Muscular Atrophy. Presented at AAN 2014*Study is now complete; data presented above is for first 3 cohorts, 12 mg data cohort not yet available (as of May 2015)



ISIS-SMNRx Phase 3 Study (ENDEAR)*

A Phase 3, randomized, double-blind, sham-procedure controlled study in infants with SMA

–Global study in ~110 SMA infants ≤ 7 months old with 2 copies of SMN2

–13 month study duration

Evaluate the efficacy and safety of ISIS-SMNRx

–Primary efficacy endpoint is time to death/permanent ventilation

–Additional efficacy endpoints include CHOP INTEND and motor milestones

Initiated - August 2014

Darras, B et al. Interim Results of a Phase 2 Study of ISIS-SMNRx in Children with Spinal Muscular Atrophy. Presented at AAN 2014*Link to study details at https://clinicaltrials.gov/ct2/show/NCT02193074?term=ENDEAR&rank=1

https://clinicaltrials.gov/ct2/show/NCT02193074?term=ENDEAR&rank=1

https://clinicaltrials.gov/ct2/show/NCT02193074?term=ENDEAR&rank=1



ISIS-SMNRx Phase 3 Study (CHERISH)*

A Phase 3, Randomized, Double-blind, Sham-Procedure Controlled Study in Children with SMA

–Global study in ~120 SMA children with SMA

–15 month study duration

Determine the efficacy and safety of ISIS-SMNRx

–Primary endpoint is change in Hammersmith motor function score

Initiated - 2014

Darras, B et al. Interim Results of a Phase 2 Study of ISIS-SMNRx in Children with Spinal Muscular Atrophy. Presented at AAN 2014*Link to study details at https://clinicaltrials.gov/ct2/show/NCT02292537?term=CHERISH&rank=2

https://clinicaltrials.gov/ct2/show/NCT02292537?term=CHERISH&rank=2

https://clinicaltrials.gov/ct2/show/NCT02292537?term=CHERISH&rank=2



Aducanumab (BIIB037)*


*BIIB037 is an investigational candidate. Efficacy and safety have not been established.



Alzheimer’s Disease (AD)

1. 2014 Alzheimer’s Disease Facts and Figures. 2. Alzheimer’s Disease International 2010. 3. http://www.nia.nih.gov/alzheimers/topics/treatment*All trademarks for drugs mentioned are the property of their respective owners

Prevalence–Alzheimer’s disease (AD) is the most common cause of dementia, accounting for 60% to 80%

of all cases1

–Estimated that 5.2 million Americans suffer from dementia caused by AD in the US1 and 35.6 million people living with dementia worldwide2

»Estimated to increase to 115.4 million worldwide by 20502

Current Approved Treatments*–Mild to Moderate AD - ARICEPT® (Donepezil), EXELON® (Rivastigmine), RAZADYNE®

(Galantamine)

–Moderate to Severe AD - ARICEPT ® (Donepezil), NAMENDA® (Memantine)

–Current treatments regulate neurotransmitters in the brain which may help to improve thinking, memory, and speaking skills.

–However, current therapies do not modify the underlying disease process and may not be effective for all patients affected by AD2

http://www.nia.nih.gov/alzheimers/topics/treatment

http://www.nia.nih.gov/alzheimers/topics/treatment



Aducanumab (BIIB037)

• AD is defined by the presence of extracellular neuritic

plaques (NPs) containing amyloid beta (Aβ) peptide

and intraneuronal neurofibrillary tangles (NFTs)

composed of tau protein in the brain1

• BIIB037 is a human monoclonal antibody that targets

aggregated forms of beta amyloid

• Therapeutic rationale: Clearance of aggregated Aβ in

the brain will attenuate the neurodegenerative

process and slow the clinical progression of AD2

1. Hardy and Selkoe. Science. 2002; 197(5580):353-356 , 2 Data on File. Biogen.



Aducanumab (BIIB037)*

• Recently completed a pre-specified interim analysis of Phase 1b

• Phase 1b study is a randomized blinded placebo controlled ascending dose study in prodromal and mild AD patients who are also amyloid positive in the brain at baseline

• Interim analysis indicated that BIIB037 reduced amyloid levels in a dose and time dependent fashion. Other preliminary findings:

–Statistically significant effect on cognition at 54 weeks

–Most significant safety findings have been amyloid-related imaging abnormalities (ARIAs). These events appear to be both dose and ApoE4 dependent, largely mild to moderate and self-resolving

• Continuing the current Phase 1b study in a blinded fashion

• Preparing to implement Phase 3 program

*As of May 2015Data on File. Biogen



Aducanumab (BIIB037) Interim Phase 1B AnalysisEffect on Mini Mental State Examination (MMSE)

*P<0.05 vs placebo

MMSE = mini-mental state examination; SE = standard error

MMSE is an exploratory endpoint. Analyses based on observed data. ANCOVA for change from baseline with factors of treatment, laboratory ApoE ε4 status (carrier and non-carrier), and baseline MMSE. Efficacy analysis population is defined as all randomized subjects who received ≥1 dose of study medication and had ≥1 post-baseline questionnaire assessment.

Sevigny J, et al. Randomized, Double-blind, Placebo-controlled, Phase 1b Study of Aducanumab (BIIB037), an Anti-Aβ Monoclonal Antibody, in Patients With Prodromal or Mild Alzheimer’s Disease: Interim Results by Disease Stage and ApoE ε4 Status. Presented at 2015 AAN Congress, Washington, DC.



Aducanumab (BIIB037) Interim Phase 1B AnalysisSafety Results Summary

Table 2. Summary of AEs Aducanumab

Placebo

(n=40)

1 mg/kg

(n=31)

3 mg/kg

(n=32)

6 mg/kg

(n=30)

10 mg/kg

(n=32)

Number subjects with an AE (%) 39 (98) 28 (90) 27 (84) 27 (90) 29 (91)

Number subjects with a

SAE (%) 15 (38) 3 (10) 4 (13) 4 (13) 12 (38)

Number subjects discontinuing

due to an AE (%) 4 (10) 3 (10) 2 (6) 3 (10) 10 (31)

AE = adverse event; SAE = serious adverse event

Sevigny J, et al. Randomized, Double-blind, Placebo-controlled, Phase 1b Study of Aducanumab (BIIB037), an Anti-Aβ Monoclonal Antibody, in Patients With Prodromal or Mild Alzheimer’s Disease: Interim Results by Disease Stage and ApoE ε4 Status. Presented at 2015 AAN Congress, Washington, DC.



BAN2401*


*BAN2401 is an investigational candidate. Efficacy and safety have not been established.



BAN2401• Suggested that amyloid beta (Aβ)

protofibril, an intermediate in the

aggregation process of the amyloid-β

peptide, initiates and drives the

neurodegenerative process in Alzheimer’s

disease

• BAN2401 is a humanized monoclonal

antibody that specifically targets the

protofibrillar form of Aβ1

• Currently in phase 2 expected to be

completed by 20162

• Collaboration with Eisai Co.

1. www.eisai.com/news/news201044.html, 2. www.clinicaltrials.gov NCT01767311Data on File. Biogen



BG00011*Idiopathic Pulmonary Fibrosis (IPF)

*BG00011 is an investigational candidate. Efficacy and safety have not been established.



Idiopathic Pulmonary Fibrosis (IPF)

Prevalence

–Approximately 100,000 people in the United States have IPF

–Most people diagnosed with IPF only live 3 to 5 years after diagnosis. Most common cause of death is respiratory failure1

Figure: National Heart, Lung, and Blood Institute website. “How the Lungs Work”1. United States National Library of Medicine website. “Idiopathic Pulmonary Fibrosis”



Idiopathic Pulmonary Fibrosis (IPF)• Two therapies recently approved for the treatment of IPF

–ESBRIET® (pirfenidone) was approved in the US on October 15, 2014

»The mechanism of action is unknown1

–OFEV® (nintedanib) was approved in the US on October 16th, 2014

»Nintedanib is a tyrosine kinase inhibitor (TKI) that targets growth factor receptors involved in the mechanisms by which pulmonary fibrosis occurs. It inhibits the platelet-derived growth factor (PDGFR), fibroblast growth factor receptor (FGFR), and vascular endothelial growth factor receptor (VEGFR)2

ESBRIET® is a registered trademark of Intermune. OFEV® is a registered trademark of Boehringer ingelheim1. http://www.roche.com/media/media_releases/2. http://www.boehringer-ingelheim.com/news/news_releases/press_releases/2014/16_october_2014.html



BG00011 (anti-αvβ6 mAb)• αvβ6 integrin is expressed in low levels on alveolar

epithelial cells in normal healthy adults and is tightly regulated by transforming growth factor-β (TGF-β); αvβ6 is upregulated with tissue injury

• αvβ6 blockade provides a mechanism for injury-specific attenuation of TGF-β activation, inhibiting fibrogenesis

• αvβ6 blockade provides a mechanism for injury-specific attenuation of TGF-β activity1

• BG00011 is a humanized monoclonal antibody targeting integrin αvβ6.

• BG00011, preclinically, exhibits anti-fibrotic activity in models of lung, kidney and liver disease. 2

• Phase 2 studying patients with IPF; estimated completion 20153

1. www.pffsummit.org/assets/pro_sat_1500_biogen_ppt.pdf2. BI1IB Press Release. 2009.3. wwwl.clinicaltrials.gov NCT01371305



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