Bristol Myers Squibb · 2021. 4. 23. · PASI 75 responders N/A 8 PGA-F 0/1 (BL ≥3) at W16 Rank...

AAD 2021Investor Presentation

April 23, 2021

Not for Product Promotional Use

Forward Looking Statement

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 onForm 10-Q and Form 8-K. These documents are available from the SEC, 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.

2


AAD 2021

Mary Beth HarlerSenior Vice President,

Immunology and Fibrosis

Development


• Deucravacitinib is a first-in-class selective TYK2 inhibitor

in moderate-to-severe Psoriasis, with proven differentiation

• Demonstrated efficacy superior to apremilast and

comparable to 1st generation biologics

• Favorable safety and tolerability

• Opportunity for broad applicability across a range of

immune-mediated diseases

BMS at AAD 2021: Deucravacitinib has potential to become the new oral standard of care in Psoriasis

4


Differentiated pathway inhibition demonstrated by head to head

preclinical evaluation, compared to JAK 1-3 inhibitors

Molecule designed to selectively target TYK2 through allosteric inhibition

Substantial evidence of a differentiated selective TYK2 inhibitor

Clinical

5

Mechanism

Preclinical

No clinically meaningful changes in hematologic, hepatic, or lipid lab

parameters in Ph2 PsO, Ph2 PsA, or Ph3 PsO studies


Deucravacitinib was designed to selectively inhibit TYK2 and downstream pathways IL-12, IL-23, and Type 1 IFN

6

Binds to the regulatory domain,

locking TYK2 in an inactive

conformation, selectively

inhibiting TYK2

Deucravacitinib:

TYK2

Regulatory

domain

Active

domain

Avoids JAK1-3 inhibition and

associated AE profile


Assay IC50 (nM)1

InhibitorTYK2 regulatory

domain

TYK2 active

domainJAK1 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 Deucravacitinib 0.2 >10000 >10000 >10000 >10000

In-vitro data suggest differentiated profile versus JAK 1-3 inhibitors

7

IC50=half-maximal inhibitory concentration; JAK=Janus kinase; nd=not determined; TYK=tyrosine kinase

Wrobleski 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

Deucravacitinib binding siteTY

K2

TYK2

Active site

Active domain

TY

K2

JAK1

Active site

Active domain

TY

K2

JAK2

Active site

Active domain

TY

K2

JAK3

Active site

Active domain

TY

K2

TYK2

Regulatory domain


POETYK PSO-1

(N=666)

POETYK PSO-2

(N=1020)

Two global Phase 3 trials with POETYK PSO-1 and PSO-2

*Apremilast was 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), patients were switched to deucravacitinib 6 mg QD.

• Key eligibility criteria: Adults with moderate to severe plaque psoriasis: PASI ≥12, sPGA ≥3, BSA ≥10%

• Stratified by geographic region, body weight, and prior biologic use

• 92.5% of patients in PSO-1 and 89.4% in PSO-2 completed 16 wks of deucravacitinib treatment vs 87.9% and 83.5%,

respectively, for placebo, and 86.3% and 85.4%, respectively, for apremilast

• All patients were eligible for a long-term extension study after 52 weeks of treatment and completion of study

Deucravacitinib 6 mg QDPlacebo (n=166)

Deucravacitinib 6 mg QD†<PASI 50

Apremilast 30 mg BID≥PASI 50

Titrate*Apremilast 30 mg BID* (n=168)

2:1

:1 R

andom

izati

on

Weeks 16 24 520

Deucravacitinib 6 mg QDPlacebo (n=255)

Deucravacitinib 6 mg QD

(n=511)

Deucravacitinib 6 mg QD<PASI 75

Deucravacitinib 6 mg QD<PASI 75



Placebo†

≥PASI 75

Apremilast 30 mg BID* (n=254)

≥PASI 75

2:1

:1 R

andom

izati

on

Weeks 16 24 520

1:1

Deucravacitinib 6 mg QDPlacebo†

Deucravacitinib 6 mg QD (n=332)

Primary

endpointPrimary

endpoint

Co-primary endpoints at Wk16, deucravacitinib

vs placebo:

• PASI 75

• sPGA 0/1

8


Superior PASI 75 response at Week 16 and Week 24

1 2

58.7%*†

35.1%

12.7%

69.0%†

38.1%

Deucravacitinib 6 mg QD PlaceboApremilast 30 mg BID

0

10

20

30

40

50

60

70

80

90

100

0 4 8 12 16 20 24

PA

SI 75 r

esp

onse

rate

, %

Weeks

Primary endpoint

53.6%*‡

40.2%

9.4%

59.3%†

37.8%

21

Durable response for deucravacitinib pts achieving PASI 75 at Week 24:

82.5%/81.4% maintained response at Week 52

0

10

20

30

40

50

60

70

80

90

100

0 4 8 12 16 20 24

PA

SI 75 r

esp

onse

rate

, %

Weeks

POETYK PSO-1 POETYK PSO-2Primary endpoint

9*P<0.0001 vs placebo. †P<0.0001 vs apremilast. ‡P=0.0003 vs apremilast

NRI = nonresponder imputation


Superior sPGA 0/1 response at both Week 16 and Week 24

0

10

20

30

40

50

60

70

80

90

100

0 4 8 12 16 20 24

sPG

A 0

/1 r

esp

onse

ara

te,

%

Weeks

53.6%*†

32.1%

7.2%

58.4%†

31.0%

0

10

20

30

40

50

60

70

80

90

100

0 4 8 12 16 20 24

sPG

A 0

/1 r

esp

onse

ara

te,

%

Weeks

50.3%*†

34.3%

8.6%

50.4%†

29.5%

POETYK PSO-1 POETYK PSO-2Primary endpoint Primary endpoint

10


aResponse defined as sPGA score of 0 or 1 with ≥2-point improvement from baseline.

*P<0.0001 vs placebo. †P<0.0001 vs apremilast.

sPGA: static Physician Global Assessment


0

20

40

60

80

0

20

40

60

80

0

20

40

60

80

0

20

40

60

80

1st generation

biologics

Deucravacitinib demonstrated oral-of-choice efficacy, comparable to 1st generation biologics

*PASI 75 results reflect the range of outcomes per Ph3 trial results

TNFs = adalimumab and etanercept; IL12/23 = ustekinumab

Data shown at either at Wk 12 or Wk 16 depending on availability; biologics data shown across dose levels

Not a head-to-head comparison vs 1st generation biologicsIL 12/-23TNFs

11

Oral agents

IL 12/-23Apremilast TNFsDeucravacitinib

Clinically meaningful efficacy in

PASI 75* at 16 weeks

…improves at week 24

Apremilast Deucravacitinib


Rank Endpoint vs placebo PSO-1 PSO-2

1 PASI 90 at W161

2 ss-PGA 0/1 (BL ≥3) at W16

3 sPGA 0 at W16

4 PASI 100 at W163

5 PSSD Symptom Score 0 (BL ≥1) at W16

6* DLQI 0/1 (BL ≥2) at W16

7* Time to relapse until W52 for W24

PASI 75 respondersN/A

8 PGA-F 0/1 (BL ≥3) at W16

Rank Endpoint vs apremilast PSO-1 PSO-2

1 sPGA 0/1 at W16

2 PASI 75 at W16

3 PASI 90 at W161

4 sPGA 0/1 at W24

5 PASI 75 at W24

6 PASI 90 at W242

7 CFB PSSD Symptom Score at W16

8 ss-PGA 0/1 (BL ≥3) at W16

9 sPGA 0/1 at W52 and W24 N/A

10 PASI 75 at W52 and W24 N/A

11 PASI 90 at W52 and W24 N/A

12 sPGA 0 at W16

13 PSSD Symptom Score of 0 at W16

(BL ≥1)

Effectiveness shown across endpoints

meaningful to patients:

• deep responses for skin clearance

Patient benefit consistently demonstrated across outcomes

Comparisons vs placebo Comparisons vs apremilast

12

*ex-US hierarchy only

Statistical significance achieved (all p vals ≤ 0.006)Statistical significance not achieved (all p vals ≥ 0.062)

• hard-to-target areas (e.g. scalp)

• maintenance of response over time

• quality of life1PASI 90 at W16 (PSO-1, PSO-2) = 35.8%, 27.2% 2PASI 90 at W24 (PSO-1, PSO-2) = 42.2%, 32.7%3PASI 100 at W16 (PSO-1, PSO-2) = 14.2%, 10.2%


AE category, n1, exposure-adjusted

incidence rate (EAIR) events per 100 patient-

years (PY)

POETYK integrated safety (PSO-1 and PSO-2), Wks 0-52

Placebo

n=666 (total PY; 240.9)

Deucravacitinib

n=1364 (total PY, 969.0)

Apremilast

n=422 (total PY, 221.1)

Any AEs 347, 217.9 995, 229.2 299, 281.1

Serious AEs 14, 5.7 55, 5.7 9, 4.0

AEs leading to discontinuation 23, 9.4 43, 4.4 26, 11.6

Deaths 1* 2† 1‡

Most common AEs (≥5%) in any active treatment group, n, EAIR

Nasopharyngitis 54, 22.9 229, 26.1 54, 25.9

Upper respiratory tract infection 33, 13.6 124, 13.4 27, 12.4

Headache 21, 8.6 80, 8.5 53, 26.0

Diarrhea 28, 11.6 69, 7.3 54, 26.5

Nausea 10, 4.1 20, 2.1 47, 22.9

Favorable safety & improved tolerability, consistent with the mechanism

1 Includes AEs between first dose and 30 days following last dose or rollover to long-term extension.

*One 57-year-old female patient receiving placebo experienced sudden cardiac death due to hypertensive cardiovascular disease. †One patient discontinued deucravacitinib after 4 days of treatment due to prohibited medication (leflunomide) and died 9 days later due to sepsis and heart failure. One additional death between Week 16‒52 due to hepatocellular carcinoma in a patient with a history of HCV infection and liver cirrhosis. ‡ One patient discontinued apremilast due to lung cancer after 3 months and died 1 month later due to lung cancer and gastrointestinal bleed.

13

Low rate of serious AEs, & fewer AEs leading to discontinuation vs apremilast & Pbo


No evidence of a JAK signature in lab parameters

14

0

50

100

150

200

250

300

350

400

Mean v

alu

e (

-/+ S

D)*

Weeks

8 160

Cholesterol, mg/dL

ULN

0

200

400

600

800

1000

Mean v

alu

e (

-/+ S

D)*

Weeks

8 160

Triglycerides, mg/dL

ULN

0

20

40

60

Mean v

alu

e (

-/+ S

D)†

Weeks

ALT, U/L

1 2 4 8 12 160

ULN

0

20

40

60

Mean v

alu

e (

-/+ S

D)†

Weeks

1 2 4 8 12 160

AST, U/L

ULN

100

200

300

400

Mean v

alu

e (

-/+ S

D)*

Weeks

Platelets, 109/L

1 2 4 8 12 160

LLN

125

135

145

155

165

Mean v

alu

e (

-/+ S

D)†

Weeks

Hemoglobin, g/dL

1 2 4 8 12 160

LLN‡


Not for Product Promotional Use 15

No signal for AEs of interest associated with JAK1-3

• None of the serious infections with deucravacitinib led to discontinuation

• No cases of herpes zoster with deucravacitinib were serious, systemic, or led to discontinuation

• No tuberculosis events and no opportunistic systemic infections were reported with deucravacitinib

• 1 SAE adjudicated as a VTE occurred in a patient receiving deucravacitinib who had an aortic dissection complicated by a PE

• Total exposure: deucravacitinib, 969.0 patient-years; placebo, 240.9 patient-years; apremilast, 221.1 patient-years. Most placebo-related data were obtained during Weeks 0‒16.

• ATE = arterial thromboembolic events; MACE = major adverse cardiovascular events; NMSC = nonmelanoma skin cancers; PE = pulmonary embolism; VTE = venous thromboembolism.

0.0

1.0

2.0

3.0

4.0

5.0

6.0

7.0

8.0

PBO

DEU

C

APR

PBO

DEU

C

APR

PBO

DEU

C

APR

PBO

DEU

C

APR

PBO

DEU

C

APR

PBO

DEU

C

APR

PBO

DEU

C

APR

NMSC Malignancies (non-NMSC) Serious infections Herpes Zoster ATE VTEs (PE + DVT) MACE

Est

imate

d Incid

ence R

ate

(95% C

I)

per

100 p

-yr

Through week 52


IndicationRelevant pathways

inhibited via TYK2

Clinical Program Status /

Expected Timing

Psoriasis IL-12 IL-23 Filing pending

Psoriatic Arthritis IL-12 IL-23 Beginning Ph3

Ulcerative Colitis IL-12 IL-23 Ph2 POC 2H21

Crohn’s Disease IL-12 IL-23 Ph2 POC 2022

Lupus IL-12 IL-23 Type I IFN Ph2 POC 2022+

Deucravacitinib has significant potential to be broadly applicable to a range of immune-mediated diseases

16


Deucravacitinib is a first in class selective TYK2 inhibitor with a uniquely designed MOA

17

• Superior/clinically meaningful and durable efficacy

— Superiority of deucravacitinib vs. apremilast demonstrated in both Ph3 studies

— Multiple measures of patient benefit observed

— Durable responses: >80% of PASI 75 responders at Week 24 maintained response at Week 52

•

• Significant potential to be broadly applicable to a range of


• Favorable safety— Overall AEs & SAEs comparable between deucravacitinib, apremilast, & placebo

— No clinically meaningful changes observed in lab parameters of interest

— No safety signal for VTE or other JAK-related AEs of interest

• Improved tolerability vs apremilast— Lower discontinuation rates due to AEs

— Lower rates of headache and GI


AAD 2021

Chris BoernerExecutive Vice President

Chief Commercialization Officer


TOPICALS** INJECTABLES

1st Gen PASI-75: 32-78%

Next-Gen PASI-75: 61-91%

Safety & burden considerations

Limited body surface use or

adjunctive therapy for

phototherapy and systemic

therapies

Psoriasis: unmet needs remain with current oral options

19

CURRENT ORALS***

~1.9m Patients ~0.4m Patients ~0.4m Patients

Source: Decision Resources Group PsO Report; Symphony Health Claims data 2020 (US); BMS Internal Estimates

• 2.7M moderate-to-Severe PsO treated patients*

• Only ~30% treated with systemic therapy today

• High interest in oral therapy

Otezla PASI-75: 35-40%

Tolerability concerns

*Numbers indicate patients on any prescribed treatment (topical, systemic, advanced) in G7 countries

**Includes patients treated with topicals and phototherapy only

***Includes Otezla, Methotrexate, Cyclosporine and di-methyl fumarate (primarily in Germany)


Superior efficacy vs Otezla

Favorable safety & tolerability

Ease of initiation & convenient

once-daily administration

Deucravacitinib’s superior profile positioned to become oral of choice

DeucravacitinibTOPICALS INJECTABLES

Launch focus: Become the oral of choice in moderate-to-severe PsO

Longer term: Expand the oral class by accelerating switch from topicals, delaying injectable use

20


• U.S. medical team experienced in dermatology in place

• U.S. sales force hiring to begin 2H 2021

Establish

the Profile

Deucravacitinib launch keys to success

21

• Oral of choice

• TYK2 novel pathway

Build the team

Gain access • Establish 1st line use

• Value demonstration

• Patient support services


Deucravacitinib: potentially applicable to a broad range of immune-mediated diseases

22

1.2

0.5 0.3 0.5 0.5

1.2

0.5 0.3 0.3

0.2

0.1

Psoriasis PsA Lupus UC Crohn's

U.S. EU5 JP

2029 non risk-adjusted sales potential* >$4B

Opportunity to grow the brand with new

indications across dermatology,

rheumatology, & gastroenterology

Future growth opportunities

…for many patients with

moderate-severe disease

IBD

Psoriatic

Arthritis

LupusPsoriasis

Patient #s in millions**

*Non-risk adjusted revenue potential through 2029; subject to positive registrational trials and health authority approval

**Numbers indicate patients on any prescribed treatment (topical, systemic, advanced); Lupus includes Non-LN SLE treated patients

with organ manifestation (90%) instead of moderate-severe treated population

Source: Decision Resources Group; BMS Internal Analysis


A rapidly emerging Immunology franchise

Ability to address multiple


— Psoriasis

— PSA (registrational trial initiating)

— Lupus, UC, CD (POC trials underway)

Broaden GI franchise

beyond IBD

— Ph3 initiated in EoE

Deucravacitinib

Cendakimab

Establish GI franchise with

Zeposia in IBD

— PDUFA of May 30th for UC

— Enrolling Ph3 program in CD

23

JIA

PSA

RA

MS

PSO

UC

Crohn’s

PSA

Lupus

Crohn’s

UC

JIA

PSA

RA

MS

2020

(Marketed)2021-23

(Near Term)

2024+

(Long Term)

GvHD

Marketed and potential future

launches in Immunology

Deucravacitinib

Cendakimab

JIA

PSA

RA

MS

PSO

UC

GvHD

EoE


Potential to be oral of choice in Psoriasis

• First in class, selective TYK2 inhibitor with a unique MOA

• Efficacy superior to Otezla & comparable to 1st generation biologics

• Favorable safety & improved tolerability

Psoriasis indication lays important foundation for continued growth

• Significant potential in a range of immune-mediated diseases

• Further expands growing Immunology franchise

Deucravacitinib offers superior efficacy with favorable safety in a once-daily pill

24

Strong early feedback on the profile


Please standby as we transition to the Q&A portion of our presentation

25


Q&A

26

Chris Boerner, Ph.D.

Executive VP,

Chief Commercialization Officer

Mary Beth Harler, M.D.

Senior VP,

Immunology and Fibrosis

Development

Bristol Myers Squibb · 2021. 4. 23. · PASI 75 responders N/A 8 PGA-F 0/1 (BL ≥3) at W16 Rank...

Documents

Transcript of Bristol Myers Squibb · 2021. 4. 23. · PASI 75 responders N/A 8 PGA-F 0/1 (BL ≥3) at W16 Rank...