Momenta Pharmaceuticals R&D Day

Momenta Pharmaceuticals R&D Day

October 10, 2014

Forward Looking Statements

Statements in this presentation regarding management's future expectations, beliefs, intentions, goals, strategies, plans or prospects, are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including but not limited to statements about the Company’s complex generics products, biosimilar and novel research and development programs, timing for clinical development and product candidate opportunities. Forward-looking statements can be identified by terminology such as "anticipate," "believe," "could," "could increase the likelihood," "hope," "target," "project," "goals," "potential," "predict," "might," "estimate," "expect," "intend," "is planned," "may," "should," "will," "will enable," "would be expected," "look forward," "may provide," "would" or similar terms, variations of such terms or the negative of those terms. Such forward-looking statements involve known and unknown risks, uncertainties and other factors referred to in the Company's Quarterly Report on Form 10-Q for the quarter ended June 30, 2014 filed with the Securities and Exchange Commission under the section "Risk Factors," as well as other documents that may be filed by Momenta from time to time with the Securities and Exchange Commission. As a result of such risks, uncertainties and factors, the Company's actual results may differ materially from any future results, performance or achievements discussed in or implied by the forward-looking statements contained herein. Momenta is providing the information in this presentation as of this date and assumes no obligations to update the information included in this presentation or revise any forward-looking statements, whether as a result of new information, future events or otherwise.

2

Momenta R&D Day Agenda

8:30 Welcome

8:45 Necuparanib (M402), a Novel, Rationally Designed, Oncology Drug Candidate Under Investigation in Metastatic Pancreatic Cancer

9:20 Necuparanib Q&A

9:30 Break

9:45 Biosimilars and Potentially Interchangeable Biologics

10:30 Biosimilars Q&A

10:40 Novel Autoimmune Drugs

11:15 Novel Autoimmune Drugs Q&A

11:25 Closing Remarks and Final Q&A

4

New Drugs Research Preclinical Clinical NDA/BLA

NecuparanibPancreatic Cancer

NecuparanibAdditional Indication

hsIVIG

SIF3

FcRn

BiosimilarsProcess

DevelopmentPreclinical Clinical BLA

M923*

M834*

M597

M615

M706

*Momenta & Baxter

Momenta Pipeline—End of 2017

5

Management Team

Craig A. Wheeler, President and CEO• Joined Momenta in 2006• Led company through launch of first

product Lovenox®• Previously with Chiron and Merck

Michael Franken, M.D., President, Biosimilars Business and SVP• Joined Momenta in 2013• Served as SVP and CBO of Radius Health• M.D. from the University of Heidelberg,

Germany and Masters in Health Policy and Management from Harvard University’s School of Public Health

Ganesh V. Kaundinya, Ph.D., Co-Founder, CSO and SVP, Research• Co-founded Momenta in 2001• Built and leads the research organization

at Momenta• Pioneered research at MIT in the areas

of analytical techniques for complex molecules and extracellular matrix regulation of cell biology

Anthony Manning, Ph.D., Vice President, Research• Brings to Momenta 20 years of experience in

the discovery and development of novel anti-inflammatory therapeutics; leads discovery of new drugs

• Previously with Biogen Idec and Roche• Contributed to the approvals of RA biologics

Actemra® and Rituxan®

Jim Roach, M.D., CMO and SVP, Development• Joined Momenta in February 2008• Leads preclinical and clinical development and

regulatory affairs• Previously with Sepracor, Millennium

Pharmaceuticals, LeukoSite and Astra USA• Affiliated with Brigham and Women’s Hospital

since 1993; Assistant Clinical Professor of Medicine at Harvard Medical School

Richard P. Shea, CFO and SVP• Joined Momenta in 2003• Has helped Momenta raise over $380

million, including the IPO• Previously with Variagenics, Genetics

Institute and PricewaterhouseCoopers

6

Necuparanib, a Novel, Rationally Designed, Oncology Drug Candidate Under Investigation in Metastatic Pancreatic Cancer

Jim Roach, M.D.Chief Medical Officer and SVP, Development

Necuparanib: A Novel Oncology Drug Candidate

• Anticancer activity of heparins is well documented

• Necuparanib, derived from heparin, was engineered to reduce anticoagulant activity and potentiate known anticancer activity

• Phase 1 results in metastatic pancreatic cancer are encouraging and support further development

• Multi-targeted MOA of necuparanib may be applicable to many cancer indications

9

Stages of Tumor Progression and Metastasis

a) Tumor-cell proliferation

b) Tumor-cell dissociation and invasion

c) Tumor-cell adhesion and metastasis

d) Tumor angiogenesis

13

Heparins Interfere with Several Vital Steps of Tumor Progression and Metastasis

14

P-selectin, fibrin

SDF-1a, chemokines

MMPs, elastase,

heparanase

VEGF, FGF, heparanase

MMPs, elastase, heparanase

P-selectin, chemokines

FGF, PDGF,

SDF-1a,

SHH

Tumor-cell dissociation and invasion

Tumor cell-plateletadhesion

Tumor-EC adhesion

ECM binding and degradationStromal cell

migration, activation,

proliferation

Angiogenesis

Progenitor cells

Placebo(n=154)

Nadroparin for 6 wks(n=148)P

rob

abili

ty o

f su

rviv

al

Months

0 12 24 36 48 60 72 84 96

Chemotherapy(n=40)

Chemotherapy + Fragmin for 18 wks

(n=39)

Median OS 8.0 vs 13.0 months

p=0.01

Ove

rall

surv

ival

Months

0

1, 0

0,8

0,6

0,4

0,2

0.0

Clinical Evidence of Anti-Cancer Effects of Heparin: Prolongation of Survival

15

SCLC. From: Altinbas, Thromb Haemost 2004

Solid tumors. From: Klerk, J Clin Oncol 2005


p=0.021

5 10 15 20 25 30 35 40

1.0

.8

.6

.4

.2

0

CDDP+GEM (n=33)

CDDP+GEM+ Nadroparin until

disease progression (n=34)

Cu

m s

urv

ival

Months


Pancreatic. CDDP=cisplatinum

From: Icli, J Surg Oncol 2007

LMWH-(n=63)

LMWH+ (n=61)P

rob

abili

ty o

f su

rviv

al

Months after beginning of chemotherapy

0 20 40

Pancreatic. From: von Delius, Thromb Haemost

2007


p=0.0001

Median OS 6.6 vs 3.8 months in subset of

pts with metastatic disease p=0.006

0.0

0,2

0,4

0,6

0,8

1,0

0 10 20 30 40

0.0

0.2

0.4

0.6

0.8

1.0

*

*Low molecular weight heparin (LMWH)

16


“In summary, the limited evidence currently available supports the hypothesis that LMWH may indeed have a beneficial effect on survival in cancer patients.... … larger randomized studies will be required in order to confirm, and expand upon, these important initial data.”*

* From Cunningham, Blood Reviews 23 (2009) 129–135

Study Malignancy/Stage Heparin Duration Beneficial Outcomes Major Bleeding

Lebeauet al.

n=277

Small cell lung cancer –Limited and extensive

UFH –adjusted dose

5 weeks

Significant increase in median survival (317 days vs. 261 days; p = 0.01)

Subgroup analysis – beneficial effects restricted to limited-stage SCLC

N.R.

Kakkaret al.

n=385

Breast, lung, GIT, pancreas, GUT, ovary,

uterus – Advanced (stage III or IV)

Dalteparin5000 IU daily

52 weeks or until death

In patients with better prognosis –significant increase in median survival (44 months vs. 24 months; p = 0.03)

LMWH 0.5% vs. placebo 0%

Altinbaset al.n=84

Small cell lung cancer -Limited and extensive

Dalteparin5000 IU daily 18 weeks

Significant increase in median survival (13 months vs. 8 months; p = 0.01)

Subgroup analysis – beneficial effect in both extensive and limited-stage SCLC

LMWH 2.4% vs. control 0%

Klerk et al.

n=302

Breast, lung, GIT, pancreas, renal, ovary,

uterus - Advanced

Nadroparin –adjusted dose

6 weeksSignificant increase in median survival

(8 months vs. 6.6 months; p = 0.02)

LMWH 3% vs. placebo 1% (p =

0.12)

Sideraset al.

n=138

Breast, lung, colorectal, prostate - Advanced

Dalteparin5000 IU daily

104 weeks or until death

No significant effect on median survival

LMWH 6% vs. control 7%

17




• Phase 1 results in pancreatic cancer are encouraging and support further development


18

Momenta’s Core Expertise in Structural and Biological Characterization of Heparins / LMWH

19

Complex generics business built core capabilities and expertise:

• Structural understanding of heparins and LMWH

• Detailed understanding of generation and control of sugar chemistry

• Process development and scale up for routine and efficient manufacturing

U H U H U H U H U H UFH

NaO2C

NaO3SO NaO3SONHSO3Na

HO

HONHAcHOHOO

OH OH OHO

O

O O OO

O O OO

O

C5H11

OSO3NaOSO3NaOSO3NaNaO2CNaO2C

NHAc

Core Tools, Robust Characterization and Functional Data Enabled Selection of Optimized Candidate: Necuparanib

20

SAR

Different Chemistries/Process to

Engineer VariantsBiological Activity

Necuparanib: Rationally Engineered to ↓ Anticoagulant Activity and ↑Anti-Cancer Activity

Reduction of anticoagulant activity relative to LMWH enables delivery of a substantially higher dose of necuparanib to further

potentiate anti-cancer effects of heparins

21

In vitro Activity of Necuparanib Against Key Heparin Binding Proteins

Compound

anti-Xa1 anti-IIa FGF VEGF SDF-1α P-sel/ PSGL1Heparanase Inhibition

IU/mg IU/mgKD

(ng/mL)KD

(ng/mL)IC50

(ng/mL)Ki

(ng/mL)IC50

(µg/mL)

Fragmin 160 60 10.2 112.5 2537 42.4 26.6

Necuparanib 2-10 2 9.8 99.5 1021 39.5 5.5

Ratio Fragmin/

Necuparanib

16-80x

reduction

30x

reduction1.0x 1.1x 2.5x 1.1x 4.8x

Values represent averages of multiple test runs and lot numbers

22

ns: not significant, **p<0.01, ****p<0.0001ANOVA with Dunett's post test vs. Saline control

3 m

g/k

g

10

mg

/kg

B16F10 Lung Metastasis Model

0.2

0.3

0.4

0.5

0.6

0.7

Lu

ng

Wei g

ht

[g]

equivalent anti-coagulant activity

********

**

ns

ns

tumor-free

lungs

Necuparanib vs. Fragmin:B16F10 Lung Metastasis Murine Model

3 m

g/k

g

10

mg

/kg

Necuparanib Has Shown Anticancer Activity in a Variety of Preclinical Models

Orthotopic Models

Tumor Types Combination Therapy Effects

Breast cancer docetaxel, cisplatin ↓ lung metastasis

Colorectal cancer 5-FU/leucovorin, capecitabine↓ primary tumor, ↓ liver

metastasis

Ovarian cancer paclitaxel/carboplatin ↓ peritoneal carcinomatosis

Pancreatic cancer gemcitabine, Abraxane® ↓ primary tumor, ↓ invasion

Genetically Engineered Mouse Model


Pancreatic cancer gemcitabine ↑ survival ↓ metastasis

23

100

90

80

70

60

50

40

30

20

10

0

100%

90%

80%

70%

60%

50%

40%

30%

20%

10%

0%

Efficacy in Preclinical Models of Pancreatic Cancer: Genetically Engineered Mouse Model: NECU + GEM

• Increased survival with NECU + GEM vs. GEM alone

• Combination reduced the metastatic rate

Lung OnlyLiver & LungLiver Only

Soft

Tis

sue

met

asta

sis

(% o

f m

ice

)

Sal + Sal Necu + Sal Sal + GEM Necu + GEM

Per

cen

tage

su

rviv

al

Time (Days)

0 50 60 70 80 90 100 110

Necuparanib SC + Gemcitabine IPSaline SC + Gemcitabine IPNecuparanib SC + Saline IPSaline SC + Saline IP

Saline vs. Gemcitabine | p= 0.0876 HR: 0.54 (0.18-1.05)Saline vs. Necuparanib + Gemcitabine | p= 0.0029 HR: 0.36 (0.07-0.50)

Gemcitabine vs. Necuparanib + Gemcitabine | p= 0.0488 HR: 0.54 (0.23-0.94)

24

Pri

mar

y tu

mo

r w

eig

ht

(g)

Efficacy in Preclinical Models of Pancreatic Cancer: AsPC-1 Orthotopic Model

Primary tumors were smallest with necuparanib combined with GEM and ABX

p<0.01 for Saline vs. GEM/ABX/Necu

Saline Necu(40 mg/kg)

GEM (30 mg/kg)ABX (20 mg/kg)

GEM/ABX/Necu0.0

0.5

1.0

1.5

2.0

2.5

25

Necuparanib: Selected Posters and Peer-reviewed Publications

26

Necuparanib: Selected Posters – Pancreatic Cancer

27






28

Study Design:Part A is an open-label, multiple

ascending dose patient study of

necuparanib given first as a single dose

and then daily in combination with ABX

and GEM. It will be conducted to

evaluate the safety and tolerability of

necuparanib alone and in combination

with ABX and GEM and to recommend a

necuparanib dose regimen for evaluation

in Part B.

Part B is a randomized, PBO-controlled,

double-blind study investigating the

antitumor activity of NECU + ABX + GEM

compared with PBO + ABX + GEM.

Protocol MOM-M402-103: Part A

29

• 8 U.S. trial sites

• Phase 1 primary objectives:

• Safety of NECU in combination with ABX + GEM

• Establish dose to take forward into Phase 2

• Other Phase 1 objectives:

• Evaluate PK, PD, biomarkers, antitumor activity

• Phase 2, randomized, controlled, POC trial initiated

(ClinicalTrials.gov Identifier NCT01621243)

Phase 1/2 Study in Metastatic Pancreatic Cancer

30

• Mean age: 65.1 yrs

• Sex: F: 26/37 (70.3%) / M: 11/37 (29.7%)

• Race: White: 33/37 (89.2%) / Black or African American: 2/37 (5.4%) / Not reported: 2/37 (5.4%)

• Ethnicity: Hispanic or Latino: 6/37 (16.2%) / Not Hispanic or Latino: 29/37 (78.4%) / Not reported: 2/37 (5.4%)

**Cohort 1*0.5 mg/kg

n=8

Cohort 21 mg/kg

n=4

Cohort 31 mg/kg

n=4

Cohort 42 mg/kg

n=5

Cohort 54 mg/kg

n=4

Cohort 6**6 mg/kg

n=4

Cohort 75 mg/kg

n=8

Phase 2 Dose 5 mg/kg

NECU + GEM

NECU + ABX + GEM

n’s = pts receiving≥1 dose NECU, * DLT of ↑LFTs, ** DLT of cellulitis; also Grade 1 ↑aPTT

Part A: Baseline Characteristics / Dose Cohort Progression

31

• No deaths considered related to necuparanib

• Three SAEs/one AE that led to discontinuation were considered possibly related

• No consistent dose relationships/patterns in individual AEs were observed

• No increases in incidence, severity or duration for known AEs of chemotherapy

AdverseEvent

Co 1*0.5mg/kg

(n=8)

Co 2*1 mg/kg

(n=4)

Co 31 mg/kg

(n=4)

Co 42 mg/kg

(n=5)

Co 54 mg/kg

(n=4)

Co 66 mg/kg

(n=4)

Co 75 mg/kg

(n=8)

Total(n=37)

Anemia 5 (63) 3 (75) 3 (75) 4 (80) 2 (50) 1 (25) 1 (13) 19 (51)

Diarrhea 2 (25) 2 (50) 1 (25) 2 (40) 3 (75) 1 (25) 0 (0) 11 (30)

Nausea 1 (13) 2 (50) 3 (75) 3 (60) 2 (50) 0 (0) 2 (25) 13 (35)

Vomiting 2 (25) 2 (50) 2 (50) 2 (40) 2 (50) 0 (0) 1 (13) 11 (30)

Fatigue 4 (50) 2 (50) 2 (50) 3 (60) 2 (50) 1 (25) 2 (25) 16 (43)

n (%) patients are shown. | *Cohorts 1 and 2 NECU + GEM / Cohorts 3-7 NECU + GEM + ABX

The most common (≥30% all patients) AEs are shown below

Part A: Most Common AEs – Irrespective of Relationship

32

33

• One cohort 1 patient was omitted; patient withdrew consent after 1 dose of necuparanib

5 1 0 1 5 2 0 2 5 3 0

2 0 0 -0 2

2 0 4 -0 5

2 0 4 -0 6

2 0 0 -0 1

2 0 4 -0 4

2 0 5 -0 3

2 0 4 -0 1

2 0 3 -0 2

2 0 4 -0 3

2 0 4 -0 2

2 0 2 -0 3

P a tie n t ID

0.5

mg

/kg

Ne

cu

+ G

em

1.0

mg

/kg

Ne

cu

+ G

em

D u ra tio n in m o n th s

O n tre a tm e n t

O ff t re a tm e n t

P ro g re s s iv e d is e a s e

O n g o in g

P F S G e m a lo n e

O S G e m a lo n e

C o h o r t

# 1

C o h o r t # 2

+ S D

S D

S D

P R

S D

+ S D

S D

S D S ta b le d is e a s e

P R P a rt ia l re s p o n s e

P D P ro g re s s iv e d is e a s e

P D

P D

P D

+

Necuparanib Part A: Patient Time on Study Cohorts 1 and 2 – NECU + GEM

34

D u ra tio n in m o n th s

5 1 0 1 5 2 0

2 0 2 -2 4

2 0 4 -1 1

2 0 2 -2 3

2 0 3 -0 4

2 0 2 -2 2

2 0 1 -0 2

2 0 2 -2 1

2 0 9 -0 4

2 0 2 -1 8

2 0 9 -0 1

2 0 2 -1 9

2 0 2 -1 6

2 0 6 -0 2

2 0 2 -1 5

2 0 0 -0 4

2 0 2 -1 4

2 0 4 -1 0

2 0 2 -1 2

2 0 2 -1 1

2 0 2 -0 8

2 0 4 -0 7

2 0 2 -0 6

2 0 4 -0 8

2 0 5 -0 5

O n tre a tm e n t

O ff t re a tm e n t

P a tie n t ID

2.0

mg

/kg

Ne

cu

+

Ge

m+

Na

b-P

4.0

mg

/kg

Ne

cu

+

Ge

m+

Na

b-P

6.0

5

.0

mg

/kg

Ne

cu

+

Ge

m+

Na

b-P

5.0

mg

/kg

Ne

cu

+

Ge

m+

Na

b-P

P ro g re s s iv e d is e a s e

O n g o in g

P F S N a b -P + G e m

O S N a b -P + G e m

C o h o r t # 3

1.0

mg

/kg

Ne

cu

+

Ge

m+

Na

b-P

C o h o r t # 4

C o h o r t # 5

C o h o r t # 6

C o h o r t # 7

S D

+ S D

+ P R

+ S D

S D

+ P R

P R

P R

+ P R

+ P R

+ P R

S D S ta b le d is e a s e

P R P a rt ia l R e s p o n s e

P D

P D P ro g re s s iv e d is e a s e

+

+

+

+

+

+

+

• Three patients were omitted because they only received one dose of necuparanib at SD1 (Cohort 4:202-10 and Cohort 7: 201-01 and 202-20)

• Eight patients (included) did not complete Cycle 1: Cohort 3 – 204-07; Cohort 4 204-10; Cohort 5 206-02; Cohort 6 209-01 and 202-18; and Cohort 7 – 201-02, 202-22, 202-23

Necuparanib Part A: Patient Time on StudyCohorts 3-7 – NECU + GEM + ABX

37

% o

f Ev

alu

able

Pat

ien

ts

Necuparanib Disease Control

11/12 (92%)

Radiographic Responses: Necuparanib, OMP-59R5

OMP-59R5 (Jan)Disease Control

10/13 (77%)

References: OMP-59R5: OncoMed press releases, Jan. 17, 2014 and Sept 29, 2014

0

20

40

60

80

100

Necuparanib OMP-59R5 (Jan) OMP-59R5 (Sep)

10/29 (34%)

14/29 (48%)

5/29 (17%)

Disease Control = CR+PR+SD / all patients

Partial Response

Stable Disease

Progressive Disease

OMP-59R5 (Sep)Disease Control

24/29 (83%)

7/12 (58%)

4/12 (33%)

1/12 (8%)

6/13 (46%)

4/13 (31%)

3/13 (23%)

CA19-9 (Biomarker) Data:Necuparanib, OMP-59R5, Celgene Ph 1/2 (ABX + GEM)

CA19-9:Most common tumor marker assessed in

pancreatic cancer patients

Predictive marker for long-term outcome and response to treatment

39

References: OMP-59R5: OncoMed press releases, Jan. 17, 2014 and Sept 29, 2014 | Celgene Ph1/2: von Hoff et al. J Clin Oncol. 2011 Dec 1;29(34):4548-54

Celgene Ph1/2:CA19-9 levels were correlated with increased survival

Patients with >50% decrease in CA19-9 levels: median PFS/OS 8.0/13.6 months

Patients with <50% decrease in CA19-9 levels: median PFS/OS 3.6/6.5 months

% o

f P

atie

nts

≥50% decreases in CA19-9 from baseline

0102030405060708090

Necuparanib OMP-59R5 (Jan) OMP-59R5 (Sep) Celgene Ph1/2

11/12 (92%)

10/13 (77%)

29/37 (78%)

95

18/25 (72%)

Study Design:Part A is an open-label, multiple

ascending dose patient study of

necuparanib given first as a single dose

and then daily in combination with ABX

and GEM. It will be conducted to

evaluate the safety and tolerability of

necuparanib alone and in combination

with ABX and GEM and to recommend a

necuparanib dose regimen for evaluation

in Part B.

Part B is a randomized, PBO-controlled,

double-blind study investigating the

antitumor activity of NECU + ABX + GEM

compared with PBO + ABX + GEM.

Protocol MOM-M402-103: Part B

40

Necuparanib Part B: Design and Anticipated Timing

EligibilityMetastatic pancreatic adenocarcinoma

Necuparanib 5 mg/kg s.c. dailyAbraxane 125 mg/m2 i.v. Days 1, 8, 15Gemcitabine 1000 mg/m2 i.v. Days 1, 8, 15

n=1481:1

Placebo s.c. dailyAbraxane 125 mg/m2 i.v. Days 1, 8, 15Gemcitabine 1000 mg/m2 i.v. Days 1, 8, 15

2014 2015 2016 2017

Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4

28-day treatment cycles

1st patientdosed

4Q 2014

Enrollment complete

1 year

Study end

2 years

Data available1H 2017

41

Necuparanib Part B: Objectives / Endpoints

Primary:• To evaluate OS in patients treated with NECU + ABX + GEM compared with placebo

(PBO) + ABX + GEM

• OS is primary endpoint

Secondary:• To evaluate PFS, response rate, and decreases in CA19-9 across groups

• To evaluate the safety and tolerability across groups

• To characterize the PK and PD profiles of NECU + ABX + GEM in a subset of patients

• To characterize the PK and PD profiles of PBO + ABX + GEM in a subset of patients

• PFS / RR / CA19-9 / PK / PD are secondary endpoints

Exploratory :• To investigate the response of various biomarkers across groups

• To investigate the incidence of thromboembolic events across groups

42


43





Significant Opportunity for “Multi-targeted” Therapeutics in Cancer

• Pathway redundancies create a therapeutic challenge

• Single-targeted drugs often show limited or short-lasting efficacy

• There is a need for drugs that can safely attenuate multiple targets/pathways

45

* From Hanahan and Weinberg Cell, 2011

* From Hanahan and Weinberg Cell, 2011Hallmarks of cancer potentially affected by necuparanib

“….we can envisage that selective co-targeting of multiple core and emerging hallmark capabilities and enabling characteristics in mechanism-guided combinations will result in more effective and durable therapies for human cancer.”*

Significant Opportunity for Necuparanib, a “Multi-targeted” Therapeutic for Cancer

47

Necuparanib Has Shown Anticancer Activity in a Variety of Preclinical Models

Orthotopic Models


Breast cancer docetaxel, cisplatin ↓ lung metastasis

Colorectal cancer 5-FU/leucovorin, capecitabine↓ primary tumor, ↓ liver

metastasis

Ovarian cancer paclitaxel/carboplatin ↓ peritoneal carcinomatosis

Pancreatic cancer gemcitabine, Abraxane® ↓ primary tumor, ↓ invasion

Genetically Engineered Mouse Model


Pancreatic cancer gemcitabine ↑ survival ↓ metastasis

48

Necuparanib Has Shown Encouraging Signals of Efficacy in Part A

49

≥50% decrease in CA19-9 from

baseline

Necuparanib: A Novel Oncology Drug Candidate Summary

• Strong biologic rationale to support documented preclinical and clinical anticancer activity of heparins• Necuparanib was rationally designed to optimize this activity

• Phase 1 trial successfully completed• Encouraging safety and early efficacy; promising Phase 2 dose determined

• Phase 2 POC trial initiated• Approx. 150 patients at 40 sites

• Necuparanib has the potential to complement both conventional chemotherapy and “targeted” therapies in a range of cancers• Planning underway for additional studies

• Orphan Drug designation granted; Fast Track designation expected to be requested Q4 2014

50

Biosimilars and Potentially Interchangeable BiologicsIntroduction

Ganesh Kaundinya, Ph.D.Co-Founder, Chief Scientific Officer and SVP, Research

Building a Broad and Diverse Biosimilars Pipeline

BiosimilarsProcess


M923 Adalimumab(Humira®)(Autoimmunity/ Inflammation)

M834 (Autoimmunity/ Inflammation)

M597

M615

M282

M706

M730 (NSO)

M740 (SP2)

54

Momenta & BaxterMomenta

Biosimilars and Potentially Interchangeable BiologicsClinical & Regulatory

Jim Roach, M.D.Chief Medical Officer and SVP, Development

56

57

58

FDA: Scientific Principles Applied to the Review of GenericLovenox are Applicable to Biosimilars

59

“…Such a “totality of the evidence” approach can also be applied to assessing biosimilars….Such strategies were used in supporting the approval of a generic low-molecular-weight heparin product, enoxaparin…. Although additional animal and clinical studies will generally be needed…. the scope and extent of such studies may be reduced further if more extensive fingerprint-like characterization is used.”

“In 2010, the FDA approved the first generic version of enoxaparin. This approval represents a major development in US regulatory science and policy that will likely affect several other complex drug products…… For example ….. the extensive analytical characterization, as carried out for enoxaparin, will be important in the evaluation of protein products and may help to reduce the scope and extent of animal and clinical studies for biosimilars.”

60

Momenta’s Goal: Elimination of Residual UncertaintyVia Thorough Characterization and Informed Process Development

Tox and ClinicalStudies, as needed

PhysicochemicalCharacterization

BiologicalCharacterization

Process Development

Thorough characterization, with additional trials if needed to address residual uncertainty. Consistent with FDA pathway, and should provide greatest economic benefit to patients and healthcare system.

61

Momenta’s Differentiated Approach is HighlyConsistent with FDA Guidance

• Deep Characterization / Integration of Data: • “Analytical studies provide the foundation….. A meaningful assessment….

depends on….the capabilities of available state-of-the-art analytical assays... Emphasis should be placed on developing orthogonal, quantitative methods”

• Potential for Reduction in Clinical Trial Requirements• “The more comprehensive and robust the comparative structural and functional

characterization are, the stronger the scientific justification for a selective and targeted approach to animal and/or clinical testing”

• “Fingerprint-like algorithm … may lead to additional bases for a more selective and targeted approach to subsequent animal and/or clinical studies”

• “The Agency has the discretion to determine that an element … is unnecessary in a 351(k) application”

• Extrapolation of Indications• The potential exists for the proposed product to be licensed for one or more

additional conditions of use….However, the sponsor will need to provide sufficient scientific justification for extrapolating clinical data”

• Interchangeability

62

Interchangeability: Momenta’s Experience with Generic Lovenox® is Relevant

63

From the ACS CAN-commissioned primer “Understanding Biologic Medicines From the Cancer Patient Perspective” January 2013.

“FDA is continuing to consider the type of information sufficient to enable

FDA to determine that a biological product is interchangeable …..”

Biosimilar Biological Product Development (BPD) Meetings Available to Sponsors

• Biosimilar initial advisory meeting: a general discussion regarding whether licensure under section 351(k)….may be feasible for a particular product, and, if so, general advice on the expected content of the development program

• BPD Type 1 Meeting: a meeting which is necessary for an otherwise stalled drug development program to proceed, a special protocol assessment meeting, or a meeting to address an important safety issue

• BPD Type 2 Meeting: to discuss a specific issue (e.g., proposed study design or endpoints) or questions where FDA will provide targeted advice regarding an ongoing program

• BPD Type 3 Meeting: is an in depth data review and advice meeting regarding an ongoing biosimilar BPD product development program. Such term includes substantive review of full study reports, FDA advice regarding the similarity between the proposed biosimilar biological product and the reference product, and FDA advice regarding additional studies, including design and analysis

• BPD Type 4 Meeting: to discuss the format and content of a biosimilar biological product application or supplement submitted under 351(k) of the PHS Act

64

FDA / EMA Harmonization Efforts Underway

65

Biosimilars and Potentially Interchangeable BiologicsScientific Approach

Ganesh Kaundinya, Ph.D.Co-Founder, Chief Scientific Officer and SVP, Research

Core Aspects of Biosimilar Platform

1. Gain deep understanding of the reference product

2. Use data to design, develop and control the process

3. Address residual uncertainty through biocharacterization

4. Integrate the data and assess similarity

68

Physico

chemical

Process

Biological

An Extensive Combination of Orthogonal Analytical Methods Provides Deep Coverage

• Full mass balance – ID all important structures in brand product

• Batch to batch variation of brand product

• Attributes that identify characteristics of cell line used

• Residual proteins that yield insights into media/purification process

69

*

*

ppm (t2)4.505.00

95.0

100.0

105.0

ppm (t1)

NW159-137-3_HSQC N-glycans T=298K 600MHz_cryo

-5

0

5

10

15

20

25

30

35

40

-100 -50 0 50 100 150 200 250 300 350

RU

Resp

on

se (

0 =

baselin

e)

sTime (0 = Sample 1 start)

… and Detects Subtle Relationships and Correlations Between Attributes

70

…QM(ox)TQ….

S SS S

...

Reference product design space






71

Physico

chemical

Process

Biological

Information from:• Publications

• Other public information

• Our analysis of multiple RPP batches(“forensic” like analysis)

• Our research on multiple cell line hosts

Correct cell line host to produce a biosimilar with fingerprint-like similarity

Cell line 1 – redCell line 2 – blueCell line 3 – blackCell line 4 - green

Genetic profiles Glycosylation profiles

Product Analytics Guides Our Cell Line Selection

72

Cwire™: Momenta Process Development Platform Designed to Achieve Fingerprint-like Similarity

74

G0G0F

G1F

G2F

HM 5

We can select clones to fit the desired product quality attributes

Cwire™

Clone 1

Clone 2

Finite number of genes, proteins and metabolites that drive protein production

Attributes Respond in a Linked Fashion During Media Optimization

76

40.0

45.0

50.0

55.0

60.0

65.0

1 6 10 8 5 3 7

0.0

1.0

2.0

3.0

4.0

5.0

6.0

7.0

8.0

1 6 10 8 5 3 7

G0F HM5

increase

decrease No change

Cwire™ provides pathway maps for balancing rational interventions to achieve desired product quality attributes

Effect of additive Effect of additive

77

78

Process optimized with Cwire™Process optimized without Cwire™

Design space

Optimized process scaled-up more than 1000-fold without changes in glycan profiles

Design space

Multifactorial Optimization of Attributes with Cwire™ Brings Them Within RPP Design Space

Maintaining PQA Through Scale-up and GMP

Bench Scale (average)Pilot Scale 1

Pilot Scale 2Pilot Scale 3

Clin/Comm Scale 1Clin/Comm Scale 2



0.0

10.0

20.0

30.0

40.0

50.0

60.0

70.0

A B C D E F G H

Q

u

a

n

t

i

t

y

Attribute

Rational control strategy enables scale-up from bench to pilot to clinical and commercial scales

maintaining quality attributes

79






80

Physico

chemical

Process

Biological

Biological Response: Appropriate and Sensitive Measures in in vitro and in vivo Systems for Comparison

81

BIOSIMILARSNEW DRUGS

ACR

DAS

CDAI

CRP

ESR

Preclinical Models: More Informative to Interrogate Complex Biology Compared to Human Clinical Trials

Disease Score

Soluble Markers

Histology Genomics

Immune Cells

MAHA & Free Drug

Orthogonal, high-resolution measurements at different disease stages provide in depth information of underlying biology for

comparison of efficacy and safety

Disease Severity

Late StageEarly Stage Mid Stage

82

Early disease: Effects on markers of

inflammation in tissue specific manner

Late disease: Effects on markers of joint

destruction, long term inflammation

Fr

ee

Dr

ug

RP

P

M9

23

Co

nt r

ol

1 0- 5

1 00

1 05

1 01 0

MA

HA

RP

P

M9

23

Co

nt r

ol

0 . 0 0 1

0 . 0 1

0 . 1

1

1 0

1 0 0

1 0 0 0

1 0 0 0 0

1 0 0 0 0 0

Ge

ne

A

RP

P

M9

23

Co

nt r

ol

- 8

- 6

- 4

- 2

0

2

Pr

ot

ein

B

RP

P

M9

23

Co

nt r

ol

0

1

2

3

4

Pr

ot

ein

C

RP

P

M9

23

Co

nt r

ol

0

5 0

1 0 0

1 5 0

2 0 0

Cli

nic

al

Sc

or

e

RP

P

M9

23

Co

nt r

ol

0

1

2

3

4

Fr

ee

Dr

ug

RP

P

M9

23

Co

nt r

ol

1 0- 5

1 00

1 05

1 01 0

MA

HA

RP

P

M9

23

Co

nt r

ol

0 . 0 0 1

0 . 0 1

0 . 1

1

1 0

1 0 0

1 0 0 0

1 0 0 0 0

1 0 0 0 0 0

Ge

ne

A

RP

P

M9

23

Co

nt r

ol

- 8

- 6

- 4

- 2

0

2

Pr

ot

ein

B

RP

P

M9

23

Co

nt r

ol

0

5

1 0

1 5

Pr

ote

in

'A'

RP

P

M9

23

Co

nt r

ol

0

2 0 0 0 0 0

4 0 0 0 0 0

6 0 0 0 0 0

Cli

nic

al

Sc

or

e

RP

P

M9

23

Co

nt r

ol

0

4

8

1 2

M923 behaves the same as HUMIRA® in multiple biological pathways over time of disease progression

Multi-tissue, Multi-parameter, Time-resolved Measurements in Information-rich Animal Models

83

84

Level 2:

Comparison of curve parameters

Level 1: Qualitative comparison of dose curves

Level 3:

Comparison of “potency” – EC50 / IC50 Level 4: Correlation to other

measurements

1.2

1.1

1.0

0.9

0.8

0.7

e.g. Hill slope

RPP M923

20

15

10

5

0

RPP M923

IC5

0 (

ng/

ml)

Pro

bab

ility

of

surv

ival

Log (Antibody) (0g/ml)

-1 0 1 2 3 4

120

80

40

0M923

RPP

In vitro: M923 Behaves the Same as HUMIRA® Across Multiple Assays and Measures






85

Physico

chemical

Process

Biological

RPP Fingerprint Defined by Combination of Physicochemical and Biological Attributes

RPPDeep

Characterization

Deep characterization across all attributes of the RPP using multiple orthogonal measures enables the identification of product

fingerprints that translate back to process design points

“Integrated Fingerprint”

BiologicalCharacterization

PhysicochemicalCharacterizationProtein

Backbone

PTMs –Glycosylation

PTMs – ProteinBackbone

Modifications

DS – HostDerived Impurities

FormulationHigher OrderStructuralProperties DP Container

Closure

DP Aggregatesand Particulates

StabilityProfile

In vitroImmunogenicity

and Safety

Pharmacokinetics

In vivo EfficacyModels

Ex vivo HumanCellular Assays

Fc-mediatedMolecular Assays

Fab-mediatedMolecular Assays

86

Totality of Evidence: Not Only a Point-by-point Comparison but Integrated View Across all Data

Momenta M923

Data Integration

Reference Product (HUMIRA)

Thousands of measures of comparison

Fingerprint-like similarity

87

(illustrative)






Physico

chemical

Process

Biological

88

Biosimilars and Potentially Interchangeable BiologicsCommercial Strategy

Michael Franken, M.D.

President, Biosimilars Business and SVP

Biosimilars: Momenta’s Commercial Strategy Overview

• Market opportunity and need

• Critical success factors

• Building competitive advantage

• Delivering on our pipeline

90

Biosimilars: Addressing an Important Need in a Large and Growing Global Market

91

0

50

100

150

200

250

300

2013 2014 2015 2016 2017 2018 2019 2020

Sale

s ($

Bill

ion

s)WW Biologics Sales: Expected To Reach $250B in 2020

ex-US US

• Biologics are the future of medicine and drive major advances in patient care

• Brand biologics are very expensive, limiting patient access

• Health care expenditures are rising to unaffordable levels

Unmet Need

• Improve patient access and level of care

• Realize significant health care cost savings

Source: Evaluatepharma, Sept 2014

Critical Success Factors

• Portfolio

• Speed and cost• Early launch

• Global markets

• Collaborative partnerships

92

Extract Maximum Value Through Collaborations

• M923 and M834 are most advanced collaboration products for certain autoimmune and inflammatory diseases

• Momenta responsible for product development to IND

• Baxter responsible for worldwide clinical development, manufacturing and commercialization

• Leveraging Baxter’s core competencies and global channel

• Baxter is committed to multi-product partnership

• Biosimilars continues to be a major area of focus and growth

93

Building a Broad and Diverse Biosimilars Pipeline

BiosimilarsProcess


M923 Adalimumab(HUMIRA®)(Autoimmunity/Inflammation)

M834 (Autoimmunity/ Inflammation)

M597

M615

M282

M706

M730 (NSO)

M740 (SP2)

94

Momenta & BaxterMomenta

Targeting brand drugs >$30B in 2013 market value

CLINICAL ADVANTAGE

REG

ULA

TOR

Y A

DV

AN

TAG

E

No

Yes

Slow Fast Time to BLA

Partial

Full

Label Extrapolation

Inter-changeability

TRADITIONAL

Clinical Trials

TRADITIONAL

MOMENTAAPPROACH

Drivers of Commercial

Success

Cost Efficient

Formulary Placement Substitution

Early Launch

Limited Clinical Program

Broad

Momenta Biosimilars: Play for the Upside Opportunity

100

Time

Po

rtfo

lio V

alu

e

Earlier Adoption

Higher Biosimilar

Conversion Rate

Higher Patient Share

Improved Patient Access

More Affordable

Care

TRADITIONAL APPROACH

BASE BUSINESS

MOMENTA’S APPROACHUPSIDE CASE

102

Momenta is Poised to Create Incremental Portfolio Value

• HUMIRA® (adalimumab) is a fully human anti-TNF mAb

• Largest selling therapeutic on market today with > $12B projected 2014 sales

• Transformative therapy for patients with multiple autoimmune /inflammatory conditions

• Continued growth expected from existing and new indications

WW HUMIRA sales / forecast by indication

Significant opportunity for M923 to expand patient care and alleviate cost burden

0

2,000

4,000

6,000

8,000

10,000

12,000

14,000

2012 2014 2016 2018

$ (

M)

UC AS PsA Crohn's Psoriasis RA

103

M923 (Adalimumab) is Entering the Clinic

Building Pipeline Value

Targeting brand drugs >$30B in current market value

Total Number of Momenta Biosimilars in Clinic

M923 M923

M834

BP1

2015 2016 2017

1 2 4

106

Biosimilars: Momenta’s Commercial Strategy Summary

• State-of-the-art platform capabilities in biosimilars

• Differentiated approach consistent with FDA guidance

• Poised to capture the upside opportunity

• Q4/2014 target for CTA filing of M923, our biosimilaradalimumab (HUMIRA®)

• Four pipeline assets in clinic in 2017

107

Novel Autoimmune Drugs

Tony Manning, Ph.D.

Vice President, Research

Momenta is Developing Novel Drugs for Autoimmune Diseases

• Momenta’s novel drug research is aimed at autoimmune disease

• Our drug candidates target auto-antibodies and immune complexes that drive many autoimmune diseases

• Momenta is targeting three drug candidates to enter the clinic over the next 24 months• Hyper-sialylated IVIg

• SIF3 recombinant protein

• Anti-FcRn antibody

110

Over 80 distinct diseases, 50 million Americans affected, $100B+ annual economic burden

NIH Autoimmune Diseases Coordinating Committee 2013; AARDA Report 2011

Rh

eum

ato

id A

rth

riti

s

Psoriasis Asthma IBD Multiple Sclerosis

Ankylosing Spondylitis Dermatomyositis Mysthemia GravisLupus APS

6.5 million

PATIENTS

2million

PATIENTS

13million

PATIENTS

1million

PATIENTS

370thousandPATIENTS

600thousandPATIENTS

150thousandPATIENTS

130thousandPATIENTS

70thousandPATIENTS

40thousandPATIENTS

Psoriasis Rheumatoid Arthritis Asthma IBD Multiple Sclerosis

There is an Immunologic Basis for Many Diseases

111

• More than 70 distinct diseases

• Lack of recent innovation to satisfy high unmet medical needs

• Few agents in development

• Recent innovation driving improved patient care and significant market value

• Robust pipelines but mostly incremental advances

• Unmet need exists but biological basis unclear

NMO: Neuromyelitis optica; CIDP: Chronic inflammatory demyelinating polyneuropathy; ANCA: ANCA associated vasculitis; MG: Myasthenia gravis; APS: Antiphospholipid syndrome; GBS: Guillain-Barre Syndrome; ITP: Idiopathic thrombocytopenic purpura; Sources: Orphanet, Medscape, Triangle Insights’ analysis, Health Advances’ analysis

500,0001,500,0002,500,0003,500,0004,500,0005,500,0006,500,0007,500,000 Psoriasis

Rheumatoid arthritis

Psoriatic arthritisUlcerative colitis

Crohn’sAnkylosing spondylitis

US diagnosed prevalence of 16 autoimmune indications

0

20,000

40,000

60,000

80,000

100,000

120,000

140,000

160,000Systemic lupus erythematosus

APS

MGANCA

CIDP

NMO

US

dia

gno

sed

pre

vale

nce

GBS

ITP

Pemphigus/pemphigoid

Dermatomyositis/polymyositis

Autoimmune Indications … A Tale of Two Cities

114

IVIg BenlystaNplate & Promacta

$0

$100

$200

$300

$400

$500

$600

$700

$800

$900

$1,000

$1,100

2011

2012

2013

2014

2015

2016

2017

2018

2019

2020

WW

re

ven

ue

($

M)

Anti-BAFF antibody

Chronic maintenance of SLE

Approved 2011

Incremental improvement

2013 WW sales $228M

$0

$100

$200

$300

$400

$500

$600

$700

$800

$900

$1,000

$1,100

2008

2009

2010

2011

2012

2013

2014

2015

2016

2017

2018

2019

2020

WW

re

ven

ue

($

M)

Nplate Promacta

TPO agonists

Third-line agents in ITP

Not disease-modifying

Approved 2008

Combined 2013 WW sales $718M

IgG fraction from pooled plasma of ~10K donors

Approved therapy for PID and 5 inflammatory diseases

Used in >50 other indications

2013 WW sales $6.2Bn

$0.0

$2.0

$4.0

$6.0

$8.0

$10.0

2009

2010

2011

2012

2013

2014

2015

2016

2017

2018

WW

sal

es

($B

n)

Innovation in a Low-prevalence Autoimmune Disease Creates Substantial Value

115

Auto-antibodies Mediate Disease and Are Not Targeted by Current Therapeutics

116

Auto-antibodies and immune complexes mediate tissue damage and dysfunction in

autoimmune and inflammatory disease

Therapeutic strategies that indirectly target auto-antibody production have

been only partially successful

Strategies that directly target auto-antibodies and immune complexes have

proven valuable in challenging clinical settings, but have limited utility in chronic

or maintenance settings

Anti-DNA ANCA Anti-Rho

Momenta Novel Autoimmune Drug Candidates

Hyper-sialylated IVIg

High potency alternative to IVIg

IV dosing, potential for SC

Orphan drug

Anti-FcRn antibody

Rapidly reduces circulating IgG and alters trafficking of immune complexes

IV or SC acutely, or chronically every

1-4 weeks

Orphan drug

Advancing to clinical trials in 2016

hsIVIg

Selective immunomodulator of

Fc receptors

Blockade of signaling through FcgRs, resulting in reduced activation of

immune cells


Orphan drug

SIF3Anti-FcRn

117

IVIg is a Complex Mixture of Immunoglobulins

Inconsistent and incomplete efficacy

Large doses and long IV infusion times

Side effects and long-term safety concerns from plasma-derived sourcing

Pooled IgG fraction from >10K Donors

118

IVIg is a Complex Mixture of Immunoglobulins

Glycan

Sialic acidAsn297

F(ab’)2

Fc

Sialylation of the Fc region of IgG mediates the anti-inflammatory effects of IVIg

119

Manufacturing controlsPhysicochemical analytics

A Robust and Scalable Process for Site-specific Hyper-sialylation

120

05

10152025303540

G0

FG

1F

G2

FG

0G

1 G2

G0F

+BG

lcN

Ac

G1F

+BG

lcN

Ac

G2F

+BG

lcN

Ac

A1F

1,3

A1F

1,6

A2

FG

1F+N

euA

cA

1F-L

acN

Ac

A1

1,3

A1

1,6 A2

A1F

+BG

lcN

Ac

1,3

A1F

+BG

lcN

Ac

1,6

A2F

+BG

lcN

Ac

G1F

+Neu

Ac+

BG

lcN

Ac

Re

l. a

bu

nd

ance

(%

)

IgG1

IgG2

IgG3/4

<5% hsIVIg

IVIg

0102030405060708090

G0F

G1F

G2F G

0

G1 G2

G0F

+BG

lcN

Ac

G1F

+BG

lcN

Ac

G2F

+BG

lcN

Ac

A1F

1,3

A1F

1,6

A2F

G1F

+Neu

Ac

A1F

-Lac

NA

c

A1

1,3

A1

1,6

A2

A1F

+BG

lcN

Ac

1,3

A1F

+BG

lcN

Ac

1,6

A2F

+BG

lcN

Ac

G1F

+Neu

Ac+

BG

lc…

Re

l. a

bu

nd

ance

(%

)

IgG1

IgG2

IgG3/4

> 80% hsIVIg

hsIVIg

100

200

300

400

500

21

>500

EU pharmacopeia Momenta

An

alyt

ical

dat

a re

ado

uts

Application of Momenta physicochemical analytics and manufacturing controls

Hyper-sialylation of IVIg Yields a Uniform High-activity Anti-inflammatory, Therapeutic Candidate

Maximize sialylation of Fc to maximize therapeutic effects

IVIg hsIVIg

122

Skin blistering pemphigoid modelCollagen antibody-induced arthritis model

Up to 10x Enhanced Anti-inflammatory Activity in Multiple Autoimmune Models

hsIVIg mediates enhanced anti-inflammatory activity in vivo

Mea

n a

rth

riti

s sc

ore

(±S

EM)

0

0 1 2 3 4 5 6 7 8 9 10 11Days

hsIVIg 0.1g/kg

IVIg 1g/kg

IVIg 0.1g/kg

Vehicle

1

2

3

4

5

6

7

8

9

0

3 4 5 6 7 8 9 10 11 12

Days

hsIVIg 0.1g/kg

IVIg 1 g/kg

IVIg 0.1g/kg

10

5

15

20

Aff

ecte

d b

od

y ar

ea [

%]

hsIVIg0.1g/kg

IVIg0.1g/kg

hsIVIg0.1g/kg

123

Advancing hsIVIg to Clinic Through Collaboration

Collaborative discussions ongoing

Potential for lower dose, higher potency Ig products (e.g. SC delivery)

Targeted to approved IVIg indications and other orphan autoimmune diseases

124

Proprietary IPDA algorithms

Momenta biocharacterization toolkit

Application of biocharacterization toolkit

Kawasaki’s disease study FcR biology index

Subj 1

Subj 2

Subj 3

Subj 4

Subj 5

Subj 6

-1 0 2 3 51 4

Normal range

= Pre-IVIg = Post-IVIg

IVIg Treatment Suppresses FcR biology

128

IgG Receptors Play a Key Role in Disease and Therapy

A family of receptors binding the Fc portion of IgGs

Key mediators of auto-antibody and immune complex functions

Genetic variants associated with autoimmune diseases

IgG Receptors

FcγRI FcγRIIA FcγRIIB FcγRIIC FcγRIIIA FcγRIIIB FcRn

α

β2mα-GPI

α2γαα

ITIMαα2γ

Activation Activation Activation ActivationInhibition ActivationRecycling TransportAg uptake…

129

Momenta Novel Autoimmune Drug Candidates Target IgG Receptors


α

β2mα-GPI

α2γαα

ITIMαα2γ


IgG Receptors

SIF3: Selective immunomodulator of FcRs

130


α

β2mα-GPI

α2γαα

ITIMαα2γ


SIF3: Selective immunomodulator of FcRs Anti-FcRn monoclonal antibody

IgG Receptors

Momenta Novel Autoimmune Drug Candidates Target IgG Receptors

131





Orphan drug

Anti-FcRn antibody



1-4 weeks

Orphan drug


hsIVIg


Fc receptors


immune cells


Orphan drug

SIF3Anti-FcRn

132

SIF3: Selective Immunomodulator of Fc Receptors


α

β2mα-GPI

α2γαα

ITIMαα2γ


Homogeneous recombinant Fc-derived product

IVIg-like specificity for FcgRs

Unique molecular design enhances avidity and potency to modulate FcgR

biology

Potential to be used as an alternative to IVIg

IgG Receptors

133

Macrophage phagocytosis

> 100x more potent than IVIg

SIF3: Powerful Anti-inflammatory Agent Fully Harnessing IVIg Mechanism of Action

FcgR binding

> 100x increased affinity than IVIg

mM

nM

SIF3 replicates efficacy of IVIg at significantly lower doses

IVIg

SIF

n g / m l%

in

hib

itio

n

1 0- 2

1 00

1 02

1 04

0

2 0

4 0

6 0

8 0

1 0 0

I V Ig

S I F 3

F c - B l o c k - P o s c o n t r o l

I C 5 0

6 2 9 n g / m l

6 n g / m l

134

ITP model

SIF3: Powerful Anti-inflammatory Agent Fully Harnessing IVIg Mechanism of Action

Arthritis model

> 50x more potent than IVIg

SIF3 replicates efficacy of IVIg at significantly lower doses

Controls IVIg SIF3

Pla

tele

t 1

09 /

L

900

600

300

0

25mg/kg

50mg/kg

100mg/kg

135





Orphan drug

Anti-FcRn antibody



1-4 weeks

Orphan drug


hsIVIg


Fc receptors


immune cells


Orphan drug

SIF3Anti-FcRn

136

Anti-FcRn Antibody


α

β2mα-GPI

α2γαα

ITIMαα2γ


Fully human monoclonal antibody targeting FcRn

Inhibits human IgG binding to FcRn resulting in rapid clearance of IgG

Potential to use acutely or intermittently to rapidly halt pathogenic processes

mediated by IgG auto-antibodies

Optimized utilizing AnaptysBio technology

IgG Receptors

137

Inhibition of IgG binding to FcRn

Anti-FcRn Antibody: High Affinity, Potent Blockade of IgG Binding to FcRn

138

Antibody IC50 (nM)

Starting mAb 48.9

mAb1 5.8

mAb2 5.7

Optimized mAb

FcRn binding by SPR

>10x improved

KD = 29 pM

KD = 436 pM

Starting mAb

Application of AnaptysBio technology

140

120

100

80

60

40

20

0

-20-100 -50 0 50 100 150 200 250 300 350

160

140

120

100

80

60

40

20

0

-20-100 0 100 200 300 400 500 600 700 800

MFI

Antibody (nM)

0.1 1 10 100

20000

15000

10000

5000

0

Control lgGStarting mAbmAb1mAb2mAb3

10x improved

Serum IgG levels

5 mpk, day 1,2,3

20 mpk, day 1,3

• Identified multiple antibodies that accelerate IgG clearance

• Rapidly decrease serum IgG levels similar to that seen with plasmapharesis

• Potent agents for exploring potential benefit in reducing auto-antibody levels in multiple autoimmune diseases

Anti-FcRn Antibody Rapidly Reduces Circulating IgG Antibodies in Non-human Primates

139

Novel Drug Candidates Target Auto-antibodies and Immune Complexes that Drive Many Autoimmune Diseases

Fab binding alters target function

Fc-mediated CDC, ADCC

IC depositionlocalizes inflammation

and fibrosis

IC-mediated autoantibody production amplification

Inhibit auto-antibody production and effects, enhance clearance

Selective immuno-modulator FcRs

Anti-FcRn mAb

HypersialylatedIVIg

Systemic lupus erythematosus

ANCA-associated vasculitis

Anti-GBM nephropathy

Antiphospholipid antibody syndrome

Autoimmune hemolytic anemia

CIDP

Dermatomyositis/polymyositis

Guillain-Barre syndrome

Idiopathic thrombocytopenia purpura

Myasthenia gravis

Neuromyelitis optica

Pemphigus

Sjogren’s syndrome

Vasculitis

…..

….. and potentially subsets of

psoriasis, RA, psoriatic arthritis, etc.

CDC=complement-dependent cytotoxicity ADCC=Antibody-dependent cellular cytotoxicity IC= Immune complex

140

Potential Positioning of Momenta TherapeuticsA

ctiv

ity

Flare (worrisome lab, inflammation)

Remission

Chronic activity

Flare (ongoing IC-mediated damage)

Flare (worrisome lab, inflammation)

TIME

Projected positioning of

MNTA therapeutics

Anti-FcRn hsIVIg/SIF3

Anti-FcRnAnti-FcRn SIF3

Current SOC(example:

lupus nephritis) CS

MMF HCQ MMF CTX/RTX/PE/IVIG AZA/MMF/RTX

CS: corticosteroids; MMF: mycophenolate; RTX: rituximab; CTX: cyclophosphamide; PE: plasma exchange; AZA: azathioprine; HCQ: hydroxychloroquine

Diseases mediated by pathogenic auto-antibodies follow a relapsing-remitting course

Different drugs for different patient needs throughout disease course

141


142




Orphan drug

Anti-FcRn antibody



1-4 weeks

Orphan drug


hsIVIg


Fc receptors


immune cells


Orphan drug

SIF3Anti-FcRn

Closing Remarks

Craig Wheeler

President and Chief Executive Officer




hsIVIG

SIF3

FcRn

BiosimilarsProcess


M923 Adalimumab(HUMIRA®)*

M834*

M597

M615

M706

Momenta Pipeline—End of 2015Clinical-stage Programs Expected to Increase from One to Three

*Momenta & Baxter

145




hsIVIG

SIF3

FcRn

BiosimilarsProcess



M834*

M597

M615

M706

Momenta Pipeline—End of 2016Clinical-stage Programs Expected to Double from Three to Six

*Momenta & Baxter

146




hsIVIG

SIF3

FcRn

BiosimilarsProcess



M834*

M597

M615

M706

*Momenta & Baxter

Momenta Pipeline—End of 2017Clinical-stage Programs Increase from Six to Nine

147

Momenta Pharmaceuticals R&D Day

October 10, 2014

Documents

Momenta Pharmaceuticals R&D Day