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Momenta Pharmaceuticals R&D Day
October 10, 2014
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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.
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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
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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
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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
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Necuparanib, a Novel, Rationally Designed, Oncology Drug Candidate Under Investigation in Metastatic Pancreatic Cancer
Jim Roach, M.D.Chief Medical Officer and SVP, Development
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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
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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
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Heparins Interfere with Several Vital Steps of Tumor Progression and Metastasis
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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
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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
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SCLC. From: Altinbas, Thromb Haemost 2004
Solid tumors. From: Klerk, J Clin Oncol 2005
Median OS 6.6 vs 8.0 months
p=0.021
5 10 15 20 25 30 35 40
1.0
.8
.6
.4
.2
0
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CDDP+GEM (n=33)
CDDP+GEM+ Nadroparin until
disease progression (n=34)
Cu
m s
urv
ival
Months
Clinical Evidence of Anti-Cancer Effects of Heparin: Prolongation of Survival
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
Median OS 5.5 vs 13.0 months
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)
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Clinical Evidence of Anti-Cancer Effects of Heparin: Prolongation of Survival
“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%
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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 pancreatic cancer are encouraging and support further development
• Multi-targeted MOA of necuparanib may be applicable to many cancer indications
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Momenta’s Core Expertise in Structural and Biological Characterization of Heparins / LMWH
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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
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Core Tools, Robust Characterization and Functional Data Enabled Selection of Optimized Candidate: Necuparanib
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SAR
Different Chemistries/Process to
Engineer VariantsBiological Activity
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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
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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
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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
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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
Tumor Types Combination Therapy Effects
Pancreatic cancer gemcitabine ↑ survival ↓ metastasis
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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)
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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
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Necuparanib: Selected Posters and Peer-reviewed Publications
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Necuparanib: Selected Posters – Pancreatic Cancer
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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
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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
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• 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
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• 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
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• 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
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• 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
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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
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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%)
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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%)
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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
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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
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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
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Necuparanib: A Novel Oncology Drug Candidate
43
• 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
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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
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* 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
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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
Tumor Types Combination Therapy Effects
Pancreatic cancer gemcitabine ↑ survival ↓ metastasis
48
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Necuparanib Has Shown Encouraging Signals of Efficacy in Part A
49
≥50% decrease in CA19-9 from
baseline
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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
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Biosimilars and Potentially Interchangeable BiologicsIntroduction
Ganesh Kaundinya, Ph.D.Co-Founder, Chief Scientific Officer and SVP, Research
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Building a Broad and Diverse Biosimilars Pipeline
BiosimilarsProcess
DevelopmentPreclinical Clinical BLA
M923 Adalimumab(Humira®)(Autoimmunity/ Inflammation)
M834 (Autoimmunity/ Inflammation)
M597
M615
M282
M706
M730 (NSO)
M740 (SP2)
54
Momenta & BaxterMomenta
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Biosimilars and Potentially Interchangeable BiologicsClinical & Regulatory
Jim Roach, M.D.Chief Medical Officer and SVP, Development
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56
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57
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58
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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.”
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60
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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
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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
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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 …..”
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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
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FDA / EMA Harmonization Efforts Underway
65
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Biosimilars and Potentially Interchangeable BiologicsScientific Approach
Ganesh Kaundinya, Ph.D.Co-Founder, Chief Scientific Officer and SVP, Research
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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
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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)
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… and Detects Subtle Relationships and Correlations Between Attributes
70
…QM(ox)TQ….
S SS S
...
Reference product design space
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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
71
Physico
chemical
Process
Biological
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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
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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
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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
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77
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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
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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
Clin/Comm Scale 3Clin/Comm Scale 4
Clin/Comm Scale 5Clin/Comm Scale 6
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
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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
80
Physico
chemical
Process
Biological
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Biological Response: Appropriate and Sensitive Measures in in vitro and in vivo Systems for Comparison
81
BIOSIMILARSNEW DRUGS
ACR
DAS
CDAI
CRP
ESR
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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
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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
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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
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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
85
Physico
chemical
Process
Biological
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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
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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)
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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
Physico
chemical
Process
Biological
88
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Biosimilars and Potentially Interchangeable BiologicsCommercial Strategy
Michael Franken, M.D.
President, Biosimilars Business and SVP
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Biosimilars: Momenta’s Commercial Strategy Overview
• Market opportunity and need
• Critical success factors
• Building competitive advantage
• Delivering on our pipeline
90
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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
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Critical Success Factors
• Portfolio
• Speed and cost• Early launch
• Global markets
• Collaborative partnerships
92
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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
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Building a Broad and Diverse Biosimilars Pipeline
BiosimilarsProcess
DevelopmentPreclinical Clinical BLA
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
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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
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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
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• 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
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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
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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
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Novel Autoimmune Drugs
Tony Manning, Ph.D.
Vice President, Research
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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
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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
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• 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
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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
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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
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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
IV dosing, potential for SC
Orphan drug
SIF3Anti-FcRn
117
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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
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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
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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
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Hyper-sialylation of IVIg Yields a Uniform High-activity Anti-inflammatory, Therapeutic Candidate
Maximize sialylation of Fc to maximize therapeutic effects
IVIg hsIVIg
122
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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
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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
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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
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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
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Momenta Novel Autoimmune Drug Candidates Target IgG Receptors
FcγRI FcγRIIA FcγRIIB FcγRIIC FcγRIIIA FcγRIIIB FcRn
α
β2mα-GPI
α2γαα
ITIMαα2γ
Activation Activation Activation ActivationInhibition ActivationRecycling TransportAg uptake…
IgG Receptors
SIF3: Selective immunomodulator of FcRs
130
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FcγRI FcγRIIA FcγRIIB FcγRIIC FcγRIIIA FcγRIIIB FcRn
α
β2mα-GPI
α2γαα
ITIMαα2γ
Activation Activation Activation ActivationInhibition ActivationRecycling TransportAg uptake…
SIF3: Selective immunomodulator of FcRs Anti-FcRn monoclonal antibody
IgG Receptors
Momenta Novel Autoimmune Drug Candidates Target IgG Receptors
131
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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
IV dosing, potential for SC
Orphan drug
SIF3Anti-FcRn
132
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SIF3: Selective Immunomodulator of Fc Receptors
FcγRI FcγRIIA FcγRIIB FcγRIIC FcγRIIIA FcγRIIIB FcRn
α
β2mα-GPI
α2γαα
ITIMαα2γ
Activation Activation Activation ActivationInhibition ActivationRecycling TransportAg uptake…
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
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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
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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
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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
IV dosing, potential for SC
Orphan drug
SIF3Anti-FcRn
136
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Anti-FcRn Antibody
FcγRI FcγRIIA FcγRIIB FcγRIIC FcγRIIIA FcγRIIIB FcRn
α
β2mα-GPI
α2γαα
ITIMαα2γ
Activation Activation Activation ActivationInhibition ActivationRecycling TransportAg uptake…
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
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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
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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
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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
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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
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Momenta Novel Autoimmune Drug Candidates
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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
IV dosing, potential for SC
Orphan drug
SIF3Anti-FcRn
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Closing Remarks
Craig Wheeler
President and Chief Executive Officer
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New Drugs Research Preclinical Clinical NDA/BLA
NecuparanibPancreatic Cancer
NecuparanibAdditional Indication
hsIVIG
SIF3
FcRn
BiosimilarsProcess
DevelopmentPreclinical Clinical BLA
M923 Adalimumab(HUMIRA®)*
M834*
M597
M615
M706
Momenta Pipeline—End of 2015Clinical-stage Programs Expected to Increase from One to Three
*Momenta & Baxter
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New Drugs Research Preclinical Clinical NDA/BLA
NecuparanibPancreatic Cancer
NecuparanibAdditional Indication
hsIVIG
SIF3
FcRn
BiosimilarsProcess
DevelopmentPreclinical Clinical BLA
M923 Adalimumab(HUMIRA®)*
M834*
M597
M615
M706
Momenta Pipeline—End of 2016Clinical-stage Programs Expected to Double from Three to Six
*Momenta & Baxter
146
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New Drugs Research Preclinical Clinical NDA/BLA
NecuparanibPancreatic Cancer
NecuparanibAdditional Indication
hsIVIG
SIF3
FcRn
BiosimilarsProcess
DevelopmentPreclinical Clinical BLA
M923 Adalimumab(HUMIRA®)*
M834*
M597
M615
M706
*Momenta & Baxter
Momenta Pipeline—End of 2017Clinical-stage Programs Increase from Six to Nine
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Momenta Pharmaceuticals R&D Day
October 10, 2014