Cardiovascular, Immunology & Fibrosis...2020/06/26 · Deep portfolio for continued innovation...
Transcript of Cardiovascular, Immunology & Fibrosis...2020/06/26 · Deep portfolio for continued innovation...
Investor SeriesImmunology & CardiovascularJune 26, 2020
Forward Looking Statement and Non-GAAP Financial Information
This presentation contains statements about the Company’s future plans and prospects that constitute forward-looking statements for purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated as a result of various important factors, including those discussed in the Company’s most recent annual report on Form 10-K and reports on Form 10-Q and Form 8-K. These documents are available on the SEC’s website, on the Bristol-Myers Squibb website or from Bristol- Myers Squibb Investor Relations.
In addition, any forward-looking statements represent our estimates only as of the date hereof and should not be relied upon as representing our estimates as of any subsequent date. While we may elect to update forward-looking statements at some point in the future, we specifically disclaim any obligation to do so, even if our estimates change.
This presentation may include certain non-generally accepted accounting principles (“GAAP”) financial measures that we use to describe our company’s performance. The non-GAAP information presented provides investors with additional useful information but should not be considered in isolation or as substitutes for the related GAAP measures. Moreover, other companies may define non-GAAP measures differently, which limits the usefulness of these measures for comparisons with such other companies. We encourage investors to review our financial statements and publicly-filed reports in their entirety and not to rely on any single financial measure. An explanation of these non-GAAP financial measures and a reconciliation to the most directly comparable GAAP financial measure are available on our website at bms.com/investors. Note that pro forma revenues in this presentation assume that the Company’s acquisition of Celgene Corporation and the Otezla® divestiture occurred on January 1, 2019. Also note that a reconciliation of certain pro forma measures, however, is not provided due to no reasonably accessible or reliable comparable GAAP measures for such pro forma measures and the inherent difficulty in forecasting and quantifying such pro forma measures that are necessary for such reconciliation.
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Investor Series
Giovanni Caforio
3
Chairman andChief Executive Officer
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Deep portfolio for continued innovation across key therapeutic areas of focus
4
Immuno-Oncology Hematology Immunology & CV
InlineBrands
Multiple LCMs
New Launches
Next Wave
Multiple myeloma
B-cell malignancies
Myeloid diseases
Otherauto-immune
diseases
Next Medicines
>20 assets with proof of concept decisions over the next three years
liso-cel CC-486ide-cel TYK2i
Relatlimab
Bempeg (NKTR-214)
CELMoD agents
T-cell engager (TCE)
Factor XIa inhib
Metastatic disease
Early stage disease
InflammatoryBowel Disease
UC - Crohn’s Lupus - Psoriatic arthritis
1L Lung, CM-9ER
Cendakimab
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Immunology & CV Development
Samit Hirawat
5
Executive VPChief Medical OfficerGlobal Drug Development
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Cell Therapy
Asset Indication
ide-cel(3)
(BCMA CAR T)MM
liso-cel(CD19 CAR T)
DLBCLFLCLLMCL
orva-cel(BCMA CAR T)
MM
bb21217(3)
(BCMA CAR T) MM
Potential first- and/or best-in-class late stage assets with significant life cycle management opportunities
6
Hematology
Asset Indication
Rebloyzl(2)
(EMA)MDSMF
Iberdomide(CELMoD agent)
MMSLE
CC-486(DNMTi)
AMLAITL
CC-92480(CELMoD agent)
MM
CC-93269(BCMA TCE)
MM
Immunology & Fibrosis
Asset Indication
TYK2Inhibitor
PsoriasisPsAUCCDSLELN
Zeposia(S1P agonist)
UCCD
Cendakimab(anti-IL-13)
EoE
HSP47 Fibrosis
Pegbelfermin(FGF-21) NASH
Cardiovascular
Asset Indication
FXIaInhibitor(4)
ThromboticDisorders
Immuno-Oncology
Asset Tumor Type
Opdivo,Yervoy(anti PD-1, anti CTLA-4)
BladderEsophageal
GastricGlioblastoma
HepatocellularHead & Neck
Melanoma Mesothelioma
NSCLCProstate
Renal
Relatlimab(anti-LAG3)
Melanoma
Bempegaldesleukin(1)
(IL-2)
BladderMelanoma
RenalMF = myelofibrosis; MM = multiple myeloma; AML = acute myeloid leukemia; AITL = angioimmunoblastic T-cell lymphoma; PsA = Psoriatic arthritis; UC = ulcerative colitis; CD = Crohn’s disease; SLE = systemic lupus erythematosus; LN = lupus nephritis
1) In partnership with NEKTAR Therapeutics, 2) in partnership with Acceleron, 3) partnership with bluebird bio, 4) In partnership with J&J
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Substantial evolution of our immunology portfolio over the next 3 years
TYK2i PsoriasisPh3 POETYK PSO (IM011-046)
TYK2iPsoriatic ArthritisPh2 (IM011-084)
Registrational
Signal Seeking
2022+20212020
TYK2i PsoriasisPh3 POETYK PSO-2 (IM011-047)
TYK2i PsoriasisPh3 (IM011-065) China-Asia
TYK2i PsoriasisPh3 (IM011-066) Japan
TYK2iSystemic lupus erythematosusPh2 PAISLEY (IM011-021)
TYK2iLupus nephritis Ph2 PAISLEY-LN (IM011-073)
TYK2iCrohn’s DiseasePh2 LATTICE (IM011-023)
ZeposiaCrohn’s DiseasePh3 Yellowstone program
ZeposiaUlcerative Colitis Ph3 TrueNorth Positive Topline
TYK2iUlcerative ColitisPh2 LATTICE (IM011-024)
ZeposiaMultiple Sclerosis FDA and EU Approval
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Cendakimab Eosinophilic EsophagitisPh3 (target start late 2020/early 2021)
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TYK2i has a novel mechanism of action that allows differentiated effects from JAK inhibitors
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ATP-binding active site
BMS-986165
Cellular IC50 (nM)1
IL-23 IFNa IL-12 EPO
Agent (TYK2/JAK2) (TYK2/JAK1) (JAK1/JAK3) (JAK2)
BMS-986165 8 5 623 >10,000
TYK2 inhibition has downstream effects on IL-12, IL-23, and Type I interferon, key cytokines in immune-mediated disease pathogenesisBMS-986165 targets a novel pseudokinase domain, which offers selective inhibition of IL-23, IFNa and IL-12
IC50=half-maximal inhibitory concentration; IFN=interferon; IL=interleukin; JAK=Janus kinase; TYK=tyrosine kinase.1. Gillooly K et al. Poster presentation at ACR/ARHP 2016. Abstract 11L.
TYK2
Activedomain
Regulatory domain (pseudokinase domain)
TYK2
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Assay IC50 (nM)1
Inhibitor TYK2 regulatory domain
TYK2 active domain JAK1 JAK2 JAK3
1 Tofacitinib nd 489 15 77 55
2 Baricitinib nd 61 4 7 787
3 Filgotinib nd 2600 363 2400 >10000
4 Upadacitinib nd 4690 47 120 2304
5 PF-06700841 nd 23 17 77 6494
6 PF-06826647 nd 17 383 74 >10000
7 BMS-986165 0.2 >10000 >10000 >10000 >10000
TYK2 inhibition: In-Vitro data suggests differentiated profile versus JAKs
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IC50=half-maximal inhibitory concentration; JAK=Janus kinase; nd=not determined; TYK=tyrosine kinaseWrobleski ST et al. J Med Chem. 2019;62(20):8973-8995; Burke JR et al. Sci Transl Med. 2019;11(502); Winthrop KL. Nat Rev Rheumatol. 2017;13:234-243
BMS-986165 binding siteTYK2
TYK2
Active site
Active domain
TYK2
JAK1
Active site
Active domain
TYK2
JAK2
Active site
Active domain
TYK2
JAK3
Active site
Active domain
TYK2
TYK2
Regulatory domain
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BMS-986165 has demonstrated proof-of-concept for TYK2 inhibition in Psoriasis
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Response rate for key products from Ph 3 trials (PASI-75)% patients at week 12 or 16
Note: ^ TYK2i data is from Ph 2, 3mg BIDSource: FDA product labels, TYK2i Phase 2 data, EvaluatePharma
6771
8289 89 91
33
69
0
20
40
60
80
100
Ph2
Small molecule
Biologic
IL-12/23 TNF IL-17 IL-23 PDE4 TYK2iTarget
Stelara Humira Cosentyx Taltz Skyrizi Tremfya Otezla TYK2i^
Robust clinical efficacy• Consistent dose response observed with sustained
efficacy after discontinuation of dosing• Efficacy in both biologic-naïve and -exposed
subjects
Validation of target and MoA• Reduction in expression of genes of the
IL-23/IL-12 and type I IFN pathways• No change in JAK1, JAK2 or JAK3 biomarkers• No dyslipidemia, liver abnormalities,
lymphopenia, or thrombotic events associated with JAK inhibitors
Ph 2 takeaways
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Phase 3 Trial designs for POETYK1 and 2
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*Apremilast is titrated from 10 mg QD to 30 mg BID over the first 5 days of dosing.†Upon relapse (≥50% loss of Week 24 PASI percent improvement from baseline), subjects will be switched to BMS-986165BID=twice daily; PASI=psoriasis area severity index; QD=every day; sPGA=static Physicians Global Assessment.1. Data on file. Princeton, NJ: Bristol-Myers Squibb Company; 2018. 2. ClinicalTrials.gov. NCT03611751. Accessed August 7, 2018.
Adults with moderate to severe psoriasis
No concomitant systemic or biologic therapy
Biologic-inadequate responders <25%
Co-primary endpoints (Week 16):– PASI-75 – sPGA 0/1
IM01
1-04
6IM
011-
047
Ran
dom
ize
Ran
dom
ize
Titrate*
BMS-986165BMS-986165Placebo
BMS-986165Placebo
16 24 52 560 Weeks
Apremilast 30 mg BID
BMS-986165
Placebo†
BMS-986165
BMS-986165
BMS-986165 BMS-986165
BMS-986165
Placebo† BMS-986165
Titrate* Apremilast 30 mg BID<PASI-75
≥PASI-75
<PASI-75
≥PASI-75
<PASI-50
≥PASI-50
Long-termrollover study
Apremilast 30 mg BID
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Core Indication Strength of Evidence TYK2 Signaling Pathways Next Data Readout
Clinical Validation
Preclinical Models
Genetic Validation
Psoriatic Arthritis IL-23 Ph2 study (2H 2020)
Systemic Lupus Erythematosus IL-12 IL-23 Type I IFN Ph2 study (2021)
Lupus Nephritis IL-12* IL-23* Type I IFN Ph2 study (2022+)
Ulcerative Colitis IL-12* IL-23 Ph 2 Mod to severe UC (2021)
Crohn’s Disease IL-12* IL-23 Ph 2 Mod to severe CD (2022+)
TYK2 inhibition has potential to impact a variety of diseases
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* Not yet validated pathways
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Zeposia: Potential to be a differentiated oral medicine in UC
• Ozanimod modulates select S1P receptors reducing reach of autoreactive lymphocytes to the gut
• No black box warning • No first dose cardiac monitoring• No broad based ocular testing• No genetic testing
• Primary endpoints of clinical remission in induction and in maintenance (p<0.0001)
• Key secondary endpoints of clinical response and endoscopic improvement
• Safety consistent with known safety profile for ozanimod and moderate to severe UC
Autoreactive lymphocyte
migration to gut
ozanimod
Favorable safety profile reflected in best-in-class MS label
First oral S1P to demonstrate benefit in moderate to severe UC in a Ph 3 study
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Zeposia Ph 3 study ongoing in Crohn’s Disease
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STEPSTONE (Ph 2)1
Primary endpoints:• Induction studies: Week 12 Clinical remission• Maintenance study: Co primary @ Week 52 Clinical remission and endoscopic response
YELLOWSTONE program (Ph 3 Study Design)
Zeposia in CD
23.2%28.1%
18.9%
0
10
20
30
40
50
60
% of
Pat
ient
s (w
k12)
Overall(n=69)
Biologic naïve(n=32)
Endoscopic Response (SES-CD decrease ≥50%) at Week 122
Zeposia
Placebo
Zeposia
Placebo
Zepo
sia
resp
onde
rs o
r re
mit
ters
are
re-
rand
omiz
ed 1
:1 t
o Ze
posi
a or
Pla
cebo
Zeposia
Placebo
52 wk maintenance study
Study 3201
Study 3202
N = 450
N = 225
N = 450
N = 225
12 wkinduction study
Adults with moderately to severely active CD
1. Feagan et al. Lancet Gastroenterol Hepatol 15-Jun 2020 online; 2. ITT-NRI analysis for SES-CDSES-CD=Simple Endoscopic Score for Crohn's Disease
Biologic experienced
(n=37)
Mean CDAI reduction at week 12 was 130 points
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Cendakimab: High unmet need in Eosinophilic Esophagitis (EoE)
• ~700K patients WW with EoE
• Life-altering GI disease with significant patient burden
— Inflammation progressing to fibrosis and narrowing of the esophagus
— Patients experience reflux and nausea/vomiting
— Risk of need for mechanical dilations to widen esophagus
• No FDA-approved therapies in the US today
— Limited treatments options include diet, PPIs, and steroid formulations
• Cendakimab has the potential to be a differentiated new treatment option
— Targets the underlying inflammation and resulting fibrosis that lead to disease progression in EoE
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White exudates
Fixed rings
Edema
Longitudinal furrows
Strictures
“Crepe paper” esophagus
Normal esophagus
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Cendakimab: Targets Key Cytokine in Pathogenesis of EoE
• High affinity IL-13 neutralizing antibody‒ Binds to the IL-13 ligand, thus inhibits
binding to IL-13Rα1 and IL-13Rα2 subunits
• Upregulated IL-13 is the key mediator of the EOE disease process1
‒ Helps eosinophil recruitment and activation‒ Disrupts epithelial barrier function
• By inhibiting both α1 and α2 subunits, cendakimab offers the potential to address both inflammation and fibrosis2
161. Caldwell et al. Curr Opin Immunol 20172. Fichtner-Feigl et al Nature Medicine VOLUME 12 NUMBER 1 ,2006
IL-13Rα1 IL-13Rα2
Cendakimab
Fibrosis & Remodeling
IL13
IL13
Inflammation
X X
Cendakimab inhibits IL-13 binding to
IL-13Rα1 & IL-13Rα2 subunits
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92.4
116.7122.6
90.3
24.8 25.5
0.0
20.0
40.0
60.0
80.0
100.0
120.0
140.0
Placebo(n=34)
RPC4046180 mg(n=31)
RPC4046360 mg(n=34)
Mea
n Es
opha
geal
Eos
inop
hil
Coun
t (c
ells
/hpf
)
P<0.0001 P<0.0001
Cendakimab Phase 2 EOE studyMeaningful reduction in eosinophil counts and endoscopic findings at Week 16
Primary Endpoint: Mean Esophageal Eosinophil Count (cells/hpf) at Week 16
Secondary Endpoint: Endoscopic EREFS
(Edema, Rings, Exudate, Furrows score) Total Score at Week 16
9.1 9.09.4
7.9
5.34.8
0.0
1.0
2.0
3.0
4.0
5.0
6.0
7.0
8.0
9.0
10.0
Placebo (N=34) RPC4046 180 mg (N=31) RPC4046 360 mg (N=34)
BL
Wk 16
P=0.0004 P<0.0001
BL WK 16 BL WK 16 BL WK 16 BL WK 16 BL WK 16 BL WK 16
Mea
n ER
EFS
Tota
l Sco
re
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Cendakimab: Acceptable Safety Profile in Phase 2 EoE study
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Placebo(N=34)n (%)
RPC4046 180 mg(N=31)n (%)
RPC4046 360 mg(N=34)n (%)
Number of Subjects Experiencing >1 TEAE 22 (65) 20 (65) 29 (85)
Headache 5 (15) 5 (16) 7 (21)
Upper respiratory tract infection 3 (9) 5 (16) 5 (15)
Arthralgia 0 4 (13) 2 (6)
Nasopharyngitis 0 3 (10) 3 (9)
Diarrhea 2 (6) 3 (10) 2 (6)
Nausea 4 (12) 2 (7) 3 (9)
Dizziness 2 (6) 3 (10) 1 (3)
Sinusitis 0 3 (10) 1 (3)
Number of Subjects Experiencing >1 Injection Site TEAE 6 (18) 4 (13) 9 (27)
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Cendakimab: Conclusions
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• New targeted therapy with potentially differentiated efficacy and safety for treatment of EoE
• Proof of Concept established, with work ongoing to support initiation of Phase 3 program in EoE
• Evaluating multiple LCM opportunities based on mechanism centrally-involved in broad span of type 2 inflammatory fibrotic diseases
Investor Series Day 3 Not for Product Promotional Use
Cell Therapy
Asset Indication
ide-cel(3)
(BCMA CAR T)MM
liso-cel(CD19 CAR T)
DLBCLFLCLLMCL
orva-cel(BCMA CAR T)
MM
bb21217(3)
(BCMA CAR T) MM
Potential first- and/or best-in-class late stage assets with significant life cycle management opportunities
20
Hematology
Asset Indication
Rebloyzl(2)
(EMA)MDSMF
Iberdomide(CELMoD agent)
MMSLE
CC-486(DNMTi)
AMLAITL
CC-92480(CELMoD agent)
MM
CC-93269(BCMA TCE)
MM
Immunology & Fibrosis
Asset Indication
TYK2Inhibitor
PsoriasisPsAUCCDSLELN
Zeposia(S1P agonist)
UCCD
Cendakimab(anti-IL-13)
EoE
HSP47 Fibrosis
Pegbelfermin(FGF-21) NASH
Cardiovascular
Asset Indication
FXIaInhibitor(4)
ThromboticDisorders
Immuno-Oncology
Asset Tumor Type
Opdivo,Yervoy(anti PD-1, anti CTLA-4)
BladderEsophageal
GastricGlioblastoma
HepatocellularHead & Neck
Melanoma Mesothelioma
NSCLCProstate
Renal
Relatlimab(anti-LAG3)
Melanoma
Bempegaldesleukin(1)
(IL-2)
BladderMelanoma
RenalMF = myelofibrosis; MM = multiple myeloma; AML = acute myeloid leukemia; AITL = angioimmunoblastic T-cell lymphoma; PsA = Psoriatic arthritis; UC = ulcerative colitis; CD = Crohn’s disease; SLE = systemic lupus erythematosus; LN = lupus nephritis
1) In partnership with NEKTAR Therapeutics, 2) in partnership with Acceleron, 3) partnership with bluebird bio, 4) In partnership with J&J
Investor Series Day 3 Not for Product Promotional Use
Substantial unmet need persistsin thrombotic diseases
Factor Xa inhibitors significantly improved efficacy and safety from previous SoC, yet further opportunity to reduce bleeding risk exists
Combining Factor Xa inhibitors with anti-plateletagents has been shown to improve outcomes but increased bleeding risk limits usage
21
Significant opportunity for an agent with comparable efficacy and reduced bleeding risk over Factor Xa inhibitors
1. McIntyre et al, Clin Card 2018; 2. Camm et al, EHJ suppl 2018; 3. Steinberg et al, JAHA 2018
Up to 20% of patients don’t receive anticoagulation, despite being at high stroke risk1
Many patients with AF receive doses lower than recommended, which may result in sub-optimal outcomes2,3
Inability to combine OACs with dual-antiplatelet therapy for neurologic/cardiac conditions
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Factor XIa inhibition has the potential to prevent thromboembolic events with a reduced risk of serious bleeding
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Extrinsic Pathway
Intrinsic Pathway
Tissue Factor
FVIIa FVII
Vesselinjury
Fibrinogen Fibrin
Common Pathway
FXII FXIIa
FIX FIXa
FX FXa
FIIFIIa
FXI FXIa
Thrombin Feedback
ApixabanRivaroxabanEdoxaban
BMS-986177
Warfarin blocks FVII, FIX, FX, and FII synthesis
DabigatranFVIIa also activates FIX (not shown)
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Factor XIa is a validated target with demonstrated efficacy and evidence for lower bleeding risk
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0
2
4
6
8
10
0
20
40
60
80
100
AspirinCOX
ClopidogrelP2Y12
AbciximabGPIIbIIIa
FactorXa Inhibitor
FactorXIa Inhibitor
Fold
Incr
ease
in
Blee
ding
Tim
e
Perc
ent
Thro
mbu
s W
eigh
t Re
duct
ion
Thrombus Weight Reduction Bleeding TimeHemophilia C is an inherited deficiency in FXI• Spontaneous bleeding is rare• Reduced risk of CV events
Retrospective cohort study of 10,193 patients including over 1200 with measured FXI deficiency:1
Antiplatelets AnticoagulantsRisk of CV events lower by
In patients with moderate-to-severe deficiency
HR 0.571
In patients with mild deficiency
HR 0.52
43%48%
Risk of VTE lower by
61%
In patients with mild deficiency
HR 0.39
No VTE eventsIn patients with moderate-to-severe deficiency1
Genetics & Epidemiology Preclinical
1 Preis et al, Blood 2017 / 2 Büller et al, NEJM 2015
Clinical
In a Phase 2 study of patients undergoing total knee arthroplasty, reduction of circulating FXI via antisense oligonucleotide provided superior reduction of VTE vs. enoxaparin and appeared safe with respect to bleeding2
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Two Phase 2 trials will inform future development path
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Total Knee Replacement (TKR) Study
FXIa inhibitor vs enoxaparin in patientsundergoing elective total knee replacementsurgery
(N=1200)
Secondary Stroke Prevention (SSP) Study
FXIa inhibitor + clopidogrel + aspirin vs. clopidogrel + aspirin in patients with acute ischemic stroke or transient ischemic attack
(N=2350)Anticipated Readouts starting in 2021 will inform potential for Ph 3 expansion in several indications
Investor Series Day 3 Not for Product Promotional Use
Key takeaways
Ongoing Opportunity to Broaden Immunology Portfolio
• Differentiated TYK2i as best in class therapy for Psoriasis with broad potential in autoimmune diseases
• Expansion opportunities for Zeposia with LCM program
— UC – positive Ph3 topline results
— CD – ongoing Ph3 trial
• Cendakimab is a potentially differentiated new treatment for EoE
— Starting Ph3 late 2020 / early 2021
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Important opportunity to renew our CV portfolio with Factor XIa
• Potential to broaden the use of antithrombotic therapy
Investor Series Day 3 Not for Product Promotional Use
Immunology & CV Commercial
26
Chris BoernerExecutive VPChief Commercialization Officer
Investor Series Day 3 Not for Product Promotional Use
Strong foundation of in-line products with opportunities for continued growth
Opportunity to grow the franchise with new medicines and new indications
In-line Portfolio
TYK2i
Zeposia IBD
Factor XIa
Strong commercial foundation including Zeposia early in its life cycle
Future Growth Opportunities
27
Cendakimab
Investor Series Day 3 Not for Product Promotional Use
Immunology market and our near term opportunity
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Immunology Context
Selective TYK2i
JIAPSARA
MS
PSOUC
Crohn’sPSA
Lupus
Crohn’s
UC
JIAPSARA
MS
2020 (Marketed)
2021-23 (Near Term)
2024+(Long Term)
GvHD
• BMS has created a successful model to compete in the RA market
• BMS built capabilities in targeted patient identification, data generation and access/reimbursement support
• Our success in Rheumatology builds a foundation for a broader set of Immunology opportunities across Derm, MS and GI
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BMS’ Marketed and Late Stage MedicineLaunches in Immunology
Cendakimab
JIAPSARA
MS
PSOUC
GvHD
EoE
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Potential to establish a strong positionin relapsing Multiple Sclerosis (MS)
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• >1M RRMS diagnosed prevalence WW (~360K US, ~415K EU5)
• In US, 3K HCPs make up 80% TRx
• HCP treatment experience drives treatment choice
• Strong patient involvement
Large concentrated market with significant patient engagement
Market: Multiple Sclerosis
• High efficacy treatment, comfortable with S1P mechanism
• Advantages on safety profile vs other S1Ps and no first-dose CV monitoring
• Fewer tests (no ophthalmic or genetic test required)
• Strong brain preservation data
• Once-daily dosing
Differentiated profile recognized by HCPs
Profile: Best-in-Class S1P
• Approved March, Launched June 1
• Medical field-based presence since 2018
• Live and virtual visits, leveraging remove engagement capabilities
• Patient engagement and best-in-class patient support
• Strong access capability
• EU: July 15 Germany product listing; HA reviews in CA, CH, AUS
US Launch 2020
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IBD: Building a Differentiated Portfolio
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Our Opportunity In IBD
~0.8
Diagnosed Prevalent
~3.1
54%
Moderate-to-SeverePrevalent
On Biologics/ Novel OralsPrevalent
46%~1.9
U.S. EU5 Diagnosed IBD Patients (2020e)
Patients (M)Ulcerative ColitisCrohn’s Disease• Large population, underserved by current
therapy options— Biologics (older TNFs and newer treatments)
are injectables and have limitations— First novel oral (JAK) reserved only
post-TNF for UC (US)
• Zeposia has the potential to be first-in-class S1P and expand oral pre- and post-biologic opportunity
• Potential for a strong GI franchise with:— Zeposia Crohn’s Ph 3: enrolling now— TYK2i and pipeline medicines
Investor Series Day 3 Not for Product Promotional Use
Potential to Play an Important Role in Ulcerative Colitis (UC)
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Relief with current options, but concerns:
• Prolonged steroid use
• Fear of injectable biologics (infections, malignancy)
• Known JAK profile – black box warning
UC Patients
• ~60% female; diagnosed around age 30
• Significant pain, flares, impact on all aspects of life and work
• Facing lifelong treatment, bowel resection
Potential to expand the oral pre- and post-biologic market with first-in-class selective S1P
• Clinically meaningful efficacy competitive with existing novel treatments (biologics)
− Highly statistically significant and consistent across clinical and endoscopic endpoints
• Differentiated safety profile
−Established safety (no black box warning) in MS with no cardiac monitoring required
• Convenient once-daily oral dosing
Investor Series Day 3 Not for Product Promotional Use
Opportunity to build a differentiated GI franchise
Establish GI franchise with Zeposia— Positive topline in UC— Enrolling Ph3 program in CD
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Novel mechanisms across immunologic disorders and strong track record of commercial success
Expand with TYK2i— POC studies underway in UC and CD
Broaden beyond IBD with Cendakimab in EoE— Ph3 to start late 2020/early 2021
TYK2i
Cendakimab
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BMS 986165(selective TYK2i)
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Moderate-Severe Psoriasis (PSO) will serveas a platform for multi-indication LCM program
• >3M diagnosed prevalence (~1.7M US, ~1.5M EU5)
• Derms are largely safety conscious
• Topicals are still widely used
• <30% moderate-to-severe PSO pts receive systemic treatment
Significant opportunity to expand oral market with best-in-class medicine
Market:Moderate-Severe Psoriasis
• Promising efficacy on skin clearance: superior to apremilast, comparable to TNFs
• Opportunity to create new SOC as pre-biologic treatment
• Novel mechanism differentiated from JAKs on safety
HCP enthusiasm for profile (Ph2)
Profile: Best Oral Option
• High medical engagement through Ph 3 enrollment
• Hire field sales and access teams following Ph 3 data
• Expand existing BMS analytics, customer and medical capabilities
Building a Dermatology Franchise
• Ph2 PSA
• Ph2 SLE
• Ph2 UC/CD
Expansion Opportunities
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Strong foundation of in-line products with opportunities for continued growth
Opportunity to grow the franchise with new medicines and new indications
In-line Portfolio
TYK2i
Zeposia IBD
Factor XIa
Strong commercial foundation including Zeposia early in its life cycle
Future Growth Opportunities
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Cendakimab
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Ability to Leverage History of Strong Commercial Execution
• Consecutive CV alliances established Plavix & Eliquis as SOC antithrombotic medicines
• Eliquis provides platform for significant growth
• Factor XIa inhibitor (with Janssen) provides opportunity for next-generation antithrombotic therapy for prevention and treatment of major thrombotic conditions
— Monotherapy and/or combination with antiplatelets
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Eliquis Net Sales
$0.1 $0.8 $1.9
$3.3 $4.9
$6.4 $7.9
201920182016 20172014 20152013
WW Net Sales ($B)
• Established Eliquis as the #1 OAC globally• Continue to grow novel oral anti-coagulant (NOAC)
and OAC shares 7 years post-launch• Focus on market expansion in key markets
US Eliquis share Oral Anti-coagulant (OAC) market• NBRx: 57%, TRx: 47%1#
Factor XIa: Potential to Continue CV Leadership
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Key takeaways
Near-term opportunities
• Strong foundation with in-line portfolio
• Zeposia launched in MS with best-in-class profile (S1Ps) also enabling expansion into IBD with UC
• First-in-class TYK2i has potential to transform psoriasis treatment
• Opportunity to establish GI franchise with Zeposia, TYK2i, Cendakimab
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Future opportunities
• LCM for Zeposia and TYK2i provide expansion into areas of larger unmet need
• Substantial unmet need remains in thrombotic diseases— Phase 2 trials (Secondary Stroke Prevention & Total Knee Replacement) will
inform a range of Phase 3 development paths
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Financial Overview
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David ElkinsExecutive VPChief Financial Officer
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Multiple Value Drivers
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Significant financial flexibility
SynergyCapture
Robust LCM program
8 near term launches
Strong in-line business
6+ Next Medicines
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Future outlook supported by launches, broad and deep pipeline, and strategic business development
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• Continue to source innovation and assets from outside the company
~$20B* in revenue potential**in 2H of the decade
Significant long-term commercial opportunities
Strategic Business Development
*non-risk adjusted
• Enabled by financial strength & flexibility— Current balance sheet strength— Significant cash flow generation
Inrebic • Reblozyl • ZeposiaCC-486 • Liso-cel • Ide-cel • TYK2i
Relatlimab • CELMoD agents • Bempeg TCE (CC-93269) • Cendakimab • Factor XIa
New Launches
Next Medicines
Next Wave
6+ agents in or close to full development; each with significant commercialpotential**
Maturing early pipeline
**subject to positive registrational trials and health authority approval
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Progress on integration: On track to achieve major milestones and synergy goals
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• Aligned company vision, mission & values
• Positive employee engagement indicators
• ~90% of the organization in place globally
• Strong access to talent through presence in key biopharma hubs
•Consolidating sites globally
• Progressing procurement integration
•On track to deliver$2.5B by 2022 – 1/3 expected in 2020
Cultural Integration
Organizational Strength
Synergies
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Consistent approach to capital allocation
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Continued commitment to the dividend
Committed to reducing debt:<1.5x Debt / EBITDA by end of 2023
Future innovation through business development
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Significant flexibility to invest in innovation
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~$45B expected in free cash flow
~$10Bin debt maturities
~$12Bin dividend** paid out
~$7Bin CVR payment
Increasing strength of the balance sheet and strong excess cash flow
~$19B*Q1 2020 cash balance
over 2020-2022
*Cash includes cash, cash equivalents and marketable securities; 75% of total cash is in the U.S.**Future dividend payouts illustrated using 2020 dividend rate and requires board authorization
Investor Series Day 3 Not for Product Promotional Use
Business Development a top priority
• Business development important to source external innovation
• Consistent criteria for sourcing innovation externally:
• Focused on therapeutic areas of interest
Immuno-oncology ● Hematology ● Immunology ● Cardiovascular ● Fibrosis ● Neurology
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Strategically Aligned
ScientificallySound
FinanciallyAttractive
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Financial strength of the company
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• Strong in-line business
• 8 near term launches
• Robust LCM program
• Synergy capture
• ~$45B of expected free cash flow over the next 3 years
• De-levering to <1.5x Debt / EBITDA by 2023
• Continued commitment to the dividend
• Sourcing future innovation through Business Development
Multiple ValueDrivers
Consistent Approach to Capital Allocation
Future outlook supported by breadth of new launches, robust pipeline and financial strength
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Investor Series
Giovanni Caforio
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Chairman andChief Executive Officer
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Deep portfolio for continued innovation across key therapeutic areas of focus
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Immuno-Oncology Hematology Immunology & CV
InlineBrands
Multiple LCMs
New Launches
Next Wave
Multiple myeloma
B-cell malignancies
Myeloid diseases
Otherauto-immune
diseases
Next Medicines
>20 assets with proof of concept decisions over the next three years
liso-cel CC-486ide-cel TYK2i
Relatlimab
Bempeg (NKTR-214)
CELMoD agents
T-cell engager (TCE)
Factor XIa inhib
Metastatic disease
Early stage disease
InflammatoryBowel Disease
UC - Crohn’s Lupus - Psoriatic arthritis
1L Lung, CM-9ER
Cendakimab
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“
Well positioned for the near-term and long-term
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CURRENT
NEAR TERM
LONG TERM
Leader with Strong Set of In-line Brands
Sustainability Enabled by Internal Innovationand Business Development
Growth Driven by New Launches and LCM Expansion
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Q&A
Giovanni Caforio, M.D.Chairman,Chief Executive Officer
David ElkinsExecutive VP,Chief Financial Officer
Nadim AhmedExecutive VP,President, Hematology
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Chris Boerner, Ph.D.Executive VP,Chief Commercialization Officer
Samit Hirawat, M.D.Executive VP,Chief Medical Officer,Global Drug Development
Rupert Vessey, M.A., FRCP, D.PhilExecutive VP,President, Research & Early Development