2017 JP Morgan Healthcare Conference Howard W. …€¦ · 2017 JP Morgan Healthcare Conference...

2017 JP Morgan Healthcare Conference

Howard W. Robin

President & CEO

January 10, 2017

This presentation includes forward-looking statements regarding Nektar’s

proprietary drug candidates, the timing of the start and conclusion of ongoing

or planned clinical trials, the timing and outcome of regulatory decisions,

future availability of clinical trial data, and royalty and milestone revenue

potential. Actual results could differ materially and these statements are

subject to important risks detailed in Nektar's filings with the SEC including the

Form 10-Q filed on November 4, 2016 and the Report on Form 8-K filed on

January 10, 2017. Nektar undertakes no obligation to update forward-looking

statements as a result of new information or otherwise.

ONZEALD Metastatic Breast Cancer & Brain Metastases

NKTR-255 IL-15

Building a Biopharmaceutical Growth Company

3

Integrated R&D, Scale-Up

and Manufacturing

Capabilities

R&D Center

San Francisco, CA

Manufacturing & Scale-Up Facility

Huntsville, AL

Wholly-Owned Research &

Development Pipeline

NKTR-181 Abuse-deterrent Opioid NCE

NKTR-214 Multiple Tumor Types Combination Trials

NKTR-358 Autoimmune Disease

NKTR-262 TLR Agonist

Revenue Drivers

Partnered Portfolio

$375-450M

Annual Revenue

By 2021

R

even

ue P

ote

nti

al

2021

R&D Support Facility

Hyderabad, India

Immuno-Oncology

Pain

Immunology

Cancer Chemotherapy

Does not include US revenue for Onzeald. Company estimates, undiscounted.

Revenue from Partnered Programs Supports

Growth of Nektar

4

Ro

yalt

y A

nd

Milest

on

e P

ote

nti

al

2017 2021

$375 - 450M Annual Revenue

By 2021

2019

PEGPH20

(Halozyme)

Amikacin Inhale

(Bayer)

Cipro DPI

(Bayer)

Onzeald (EU only)

(Daiichi Sankyo)

(AstraZeneca)

(Shire)

Adynovate is a registered trademark of Shire plc.

Movantik is a registered trademark of the AstraZeneca group of companies.

NKTR-181: A Novel Opioid Poised to Transform

the Chronic Pain Market

NKTR-181 brings unique properties

to the treatment of chronic pain:

Slow rate of entry into CNS designed to

reduce euphoria and resulting abuse

liability

Designed to cause less sedation and

reduce risk of respiratory depression

Targeting C-III or better scheduling

Properties are inherent to molecule

Received Fast Track Status from FDA

5

$20 Billion+

Global Chronic Pain

Therapy Market

Opioids

$12.6B

Antiepileptics

$3.6B

Antidepressants

$1.5B

NSAIDs/COX-2s

$5.9B

Chronic pain market includes: Chronic back pain

Osteoarthritis

Fibromyalgia

Neuropathic pain

Source: 2013 IMS and Decision Resources

NKTR-181 Development Strategy

6

Pivotal Human Abuse

Liability Study Initiated

Long-term (52-wk) safety study

enrollment complete; 6 & 12-month

exposure requirements met

Discuss early NDA filing based

upon efficacy and HAL

trial results

2H 2017

Initiate additional trial(s) with

Partner to support expansion of

label and/or approval

Efficacy Study Ongoing in

Opioid-naïve Patients with

Chronic Low Back Pain

Topline Data

March 2017

Q1 2017 Q2 2017 Q3 2017

Initiate Partnering

Discussions

Q2 2017

Topline Data

Mid-2017

The Immunity Cycle and Multiple Points of

Intervention for I-O Therapies

7

4. Trafficking of

T cells to tumor

5. Infiltration

of T cells into

tumors

6. Recognition

of cancer cells

by T cells

7. Killing of

cancer cells 1. Release of

cancer cell

antigens

2. Cancer

antigen

presentation

3. Priming

and

activation

Source:

Oncology Meets Immunology: The Cancer-Immunity Cycle

Chen and Mellman

Immunity, Volume 39, Issue 1, 1 - 10

4. Trafficking of T cells

to tumor (CTLs)

5. Infiltration of T

cells into tumors

(CTLs, endothelial

cells)

6. Recognition

of cancer cells

by t cells

(CTLs, cancer

cells)

7. Killing of cancer cells

(immune and cancer

cells)

1. Release of cancer

cell antigens (cancer

cell death)

2. Cancer

antigen

presentation

(dendritic

cells/APCs)

3. Priming and

activation

(APCs & T cells)

Nektar’s Immuno-Oncology Strategy to Create

Therapies that Cover the Immunity Cycle

8

Therapies

need to be

accessible as

medicines

Target as

many steps as

possible in the

cycle with as

few therapies

as possible

3. Priming and

activation

(APCs & T cells)

6. Recognition

of cancer cells

by t cells

(CTLs, cancer

cells)


cells into tumors

(CTLs, endothelial

cells)


(immune and cancer

cells)



cell death)

2. Cancer

antigen

presentation

(dendritic

cells/APCs)



9


to tumor (CTLs)

Therapies

need to be

accessible as

medicines

Target as

many steps as

possible in the

cycle with as

few therapies

as possible

NKTR-214 (CD122 Agonist)

Prime, Proliferate, Activate &

Increase Tumor-Infiltrating

Lymphocytes (TILs), Increase PD-1

expression

NKTR-262

(TLR Agonist)

Activate Dendritic

Cell Response

NKTR-255 (IL-15)

Stimulate NK Cells,

Sustain Immune

Response & Generate

T Cell Memory

IL-2

IL-2 is Master Growth Factor for T Cells and

Natural Killer (NK) Cells

Native IL-2 has

pleiotropic effects on the

immune response

rhIL-2 protein therapy

(aldesleukin) requires

high and frequent dosing

in ICU which results in

severe side effects

10

CTLs

CD8+ T-Cells

and NK Cells

b

Stimulates Immune

Response to Kill

Tumor Cells

CD4+ Regulatory T-Cells

Tregs ab

Down-Regulates

Proliferation of CD8+ T-cells

and Suppresses Immune

Response

NKTR-214: Biasing Action to CD 122, or IL-2R

Beta, to Stimulate T-Cell Production

Biases signaling to favor

the CD122 Receptor (IL-

2Rβγ complex)

Eliminates over-activation

of IL-2 pathway that

results in serious safety

issues

Achieves antibody-like

dosing schedule in

outpatient setting

11

CTLs

CD8+ T-Cells

and NK Cells

b

NKTR-214

Stimulates Immune

Response to Kill

Tumor Cells

CD4+ Regulatory T-Cells

Tregs ab

Down-Regulates

Proliferation of CD8+ T-cells

and Suppresses Immune

Response

NKTR-214 Selectively Grows T Cells, NK Cells

Tumor Microenvironment in Cancer Patients

NKTR-214 drives immune

activation in the tumor

• Increase in total T cells, NK

and CD8 T cells

• No increase in Tregs

• Increase in PD-1 positive CD8

T cells

• Increase in newly proliferating

CD8 T cells

• Activation and expression of

anti-tumor genes

• Change in T cell clonality in

the tumor

12

Fold change expressed as Week 3 / predose

Shown are results from N=10 patients

Analysis of T cell Populations in Tumor

0

1 0

2 0

3 0

4 0

C D 8 T r e g s

0

10

20

30

40

CD8 Tregs

1.6

29.8

• BMS is global leader in immuno-oncology

• BMS and Nektar collaborating exclusively on anti-PD1 and IL-

2-based mechanisms

• Companies to conduct Phase 1/2 development of NKTR-214

and Opdivo in eight or more cancer indications

• BMS and Nektar to split clinical costs 50/50

• Nektar retains all rights to NKTR-214

• Prior to Sept. 2018, if Nektar chooses to partner NKTR-214,

BMS has right of first negotiation

• Nektar retains ability to conduct its own trials of NKTR-214

with any anti-PD1/PDL1 agents and can collaborate to run

trials with any other company outside of anti-PD1/PDL1

mechanisms

BMS and Nektar Clinical Collaboration for

NKTR-214 and Opdivo®

13 Opdivo is a registered trademark of Bristol-Myers Squibb

14

Renal Cell Carcinoma 2nd line I-O naïve, N=26

NSCLC 2nd line I-O naïve

Triple Negative BC 2nd line I-O naïve, N= 36

Melanoma 1st line

Renal Cell Carcinoma 2nd line I-O naïve

Phase 1 Dose Escalation

(on label indications)

N= 20-30

Phase 2 Expansion Cohorts

Q2 2017

Melanoma 2nd line I-O relapsed, N=26

Urothelial Carcinoma (Bladder)

1st line, cisplatin ineligible, N=44

Renal Cell Carcinoma 2nd line I-O relapsed, N=26

Melanoma 1st line, N=28

NSCLC 2nd line I-O relapsed, N=26

NSCLC 2nd line I-O naïve, N=36

New

Indication

Initial Dose Combination Arm: Group 1: 0.006 q3w NKTR-214 + 240 mg q2w nivo

q2w and q3w Parallel Dose Combination Arms:

Group 2: 0.003 q2w NKTR-214 + 240 mg q2w nivo




Group 6: 0.009 q3w NKTR-214 + 360 mg q3w nivo (optional)

PIVOT Program: NKTR-214 plus Opdivo® with

Eight Expansion Cohorts Planned

PIVOT-02 PIVOT-04

Opdivo is a registered trademark of Bristol-Myers Squibb

Small Molecules

(TLR Agonist,

other targets)

NKTR-214 Provides A Central Mechanism to Combine

with Multiple Modalities in Immuno-Oncology

15

Checkpoint

Inhibitors

Cell Therapies

(TIL therapy, ECT) Vaccines

NKTR-214:

T Cell Growth

Factor

NKTR-214: Additional Development Programs

in 2017

16

Initiate Phase 1 trial of NKTR-214 and anti-PD-L1

Initiate Phase 1/2 trial of NKTR-214 in combination with

Endogenous T Cell regimen in non-small cell lung cancer

patients expressing the MAGE-A3 antigen (with MD

Anderson)

Initiate triplet combination trial of NKTR-214 with anti-PD-1

and anti-CTLA-4 agents

Preclinical studies underway with NKTR-214 and therapeutic

tumor vaccines with potential for clinical advancement in

2017

Initiate IST in Sarcoma with NKTR-214 and Opdivo® at

Memorial Sloan Kettering and MD Anderson

Checkpoint

Inhibitors

Vaccines

Cell Therapies

(TIL therapy, ECT)

Opdivo is a registered trademark of Bristol-Myers Squibb

3. Priming and

activation

(APCs & T cells)

6. Recognition

of cancer cells

by t cells

(CTLs, cancer

cells)


cells into tumors

(CTLs, endothelial

cells)


(immune and cancer

cells)



cell death)

2. Cancer

antigen

presentation

(dendritic

cells/APCs)


Therapies That Cover the Immunity Cycle

17


to tumor (CTLs)

Therapies

need to be

accessible as

medicines

Target as

many steps as

possible in the

cycle with as

few therapies

as possible





expression

NKTR-262

(TLR Agonist)

Activate Dendritic

Cell Response

NKTR-255 (IL-15)

Stimulate NK Cells,

Sustain Immune

Response & Generate

T Cell Memory

NKTR-255: Stimulates Memory T Cell and NK

Cell Activation

IL-15 delivers T-cell survival

signal, promotes CD8 memory

cell formation and activates

Natural Killer (NK) cells with

minimal CD4 activity

• Short half-life of native IL-15

requires high and frequent dosing

with prohibitive side effects

NKTR-255 designed to

overcome native IL-15

shortcomings

IND to be filed by end of 2017

18

NKTR-255 is first

potential medicine to

access the IL-15

pathway by

preserving receptor

binding to IL-15Ra

with antibody-like

dosing

NKTR-255 Induces Sustained Signaling and Cell

Proliferation In Vivo

19 Source: Poster #342 presented at SITC 2016, National Harbor, Maryland

Single dose of NKTR-255 sustains NK and CD8 cell activation

and proliferation for more than 3 days

Effect of NKTR-255 also observed on both effector memory

and central memory CD8 cells

Mice received a single i.v. dose of 0.3 mg/kg NKTR-255 (right) or IL-15 (left), then STAT5 phosphorylation in lymphocyte

subpopulations from whole blood was assessed by flow cytometry.

IL-15 NKTR-255

3. Priming and

activation

(APCs & T cells)

6. Recognition

of cancer cells

by t cells

(CTLs, cancer

cells)


cells into tumors

(CTLs, endothelial

cells)


(immune and cancer

cells)



cell death)

2. Cancer

antigen

presentation

(dendritic

cells/APCs)



20


to tumor (CTLs)

Therapies

need to be

accessible as

medicines

Target as

many steps as

possible in the

cycle with as

few therapies

as possible





expression

NKTR-262

(TLR Agonist)

Activate Dendritic

Cell Response

NKTR-255 (IL-15)

Stimulate NK Cells,

Sustain Immune

Response & Generate

T Cell Memory

NKTR-262: Adding a Unique Intratumoral TLR

Agonist to Nektar’s Immuno-Oncology Portfolio

TLR agonists activate innate

immunity, myeloid cell response and

increase tumor antigen presentation

• Creates tumor-suppressing micro-

environment by mimicking local

infection

Nektar technology optimizes

specific abscopal effect in tumors

without systemic exposure of TLR

agonist

NKTR-262 designed to be highly

synergistic with NKTR-214

NKTR-262 with NKTR-214 represent

a novel, wholly-owned combination

regimen in immuno-oncology

21

NKTR-214

proliferates &

expands T Cells

NKTR-262

activates

innate

immunity

Dendritic

Cell M1

Macrophage

CD8+

T Cell

Present antigens

to prime T Cell

NKTR-262 0.8 mg in 40 μL volume given in a single IT dose, NKTR-214 0.8 mg/kg q9dx3 IV; N=10 per group

Complete Regression and Abscopal Effect with

Combination of NKTR-262 and NKTR-214

22

NKTR-214

D 0 D 9 D 18

NKTR-262

Primary (injected) CT-26 Colon Tumor

0 1 0 2 0 3 0 4 0 5 0

0

5 0 0

1 0 0 0

Tu

mo

r V

olu

me

(m

m3

SE

M)

D a y s a f t e r f i r s t d o s e

0 1 0 2 0 3 0 4 0 5 0

0

5 0 0

1 0 0 0

Tu

mo

r V

olu

me

(m

m3

SE

M)

D a y s a f t e r f i r s t d o s e

Vehicle

NKTR-214

NKTR-262 NKTR-262 + NKTR-214

Vehicle

NKTR-214

NKTR-262

NKTR-262 + NKTR-214

NKTR-262 + NKTR-214

NKTR-214

NKTR-262

Vehicle

Secondary (non-injected) CT-26 Colon Tumor

Survival CT-26 Colon Tumor

Primary (injected) Tumor

Secondary (non-injected) Tumor

Dosing

Auto-Immune Disease is Characterized by

Imbalance of T-Reg Cells to T-Effector Cells

23

Pathological

overpopulation of

antigen-specific

(self-reactive)

effector T cells

Insufficient

T-reg cell

population to

control the

pathological

effector T cells

Beneficial

effector T cell

population

• Current auto-immune

disease therapies work

by suppressing overall

immune system function

– Treat symptoms of the

over-active immune

system

– Do not address

underlying pathology

– Block both pathological

and beneficial effector T

cells resulting in

infection, bleeding,

cancer risks, etc.

NKTR-358: Growing the Body’s Own Population

of T-Reg Cells to Treat Auto-Immune Disease

24

Restore balance

and normalize

T-reg cell and T-

effector cell

function

What if you could grow the

body’s own population of T-

reg cells and directly treat

the underlying disease

pathology?

NKTR-358 is Selective for Enhancing of T-Reg

Proliferation and Activation in Non-Human Primates

25

• Single dose NKTR-358 produced greater Treg expansion than repeat low-dose IL-2

• In mice, NKTR-358 treatment promotes >30-fold increase in Treg suppressive activity

Teff

Treg

Dosing

NKTR-358 could be a superior approach to treating multiple auto-immune diseases

including lupus, transplant, rheumatoid arthritis, Crohn’s disease and psoriasis

1M + 1F cynomolgus monkey per treatment, both agents given at 0.025 mg/kg – single dose SC for NKTR-358 vs QDx5 SC for IL-2.

Dosing

Fold Change in Treg and Teff T-Reg Activation Markers

NKTR-358 Suppresses Antigen-Driven Inflammation

in Preclinical Model of Cutaneous Hypersensitivity

26

Sensitization (KLH flank) Elicitation in ear (with KLH)

Measure ear swelling Day 0 Day 5

Dosing begun on Day 0: NKTR-358, SC q3d, Cyclosporin A, PO qd N=10

0

2

4

6

8

1 0

1 2

1 4

1 6

T i m e a f t e r K L H c h a l l e n g e ( h )

e

ar

th

ick

ne

ss

(m

m,

me

an

S

EM

)

V e h i c l e

N K T R - 3 5 8 , 0 . 0 0 3 m g / k g

N K T R - 3 5 8 , 0 . 0 1 m g / k g

N K T R - 3 5 8 , 0 . 0 3 m g / k g

0 2 4 4 8 7 2

N K T R - 3 5 8 , 0 . 1 m g / k g

N K T R - 3 5 8 , 0 . 3 m g / k g

9 6

C y c l o s p o r i n A , 1 0 m g / k g

Cutaneous Hypersensitivity Response

NKTR-358: Phase 1 Clinical Development in

Lupus and GVHD

27

Q1-Q3 2017 Q3 2017

Initiate Phase 1b

Multiple Ascending Dose Trial in

Lupus (SLE) Patients

Multiple SQ Doses of NKTR-358 (n ~50)

• 3:1 randomization vs. placebo

• Evaluate changes in T-reg cells

and activation markers

• Establish P2 doses

Phase 1

Single Ascending Dose Trial in

Healthy Subjects

Single SQ Dose of NKTR-358 (n ~50)

• Evaluate changes in T-reg

cells (number) and activation

markers (function)

• Evaluate PK/PD to determine

dosing for multiple dose trial

Data expected in Q3 2017

Initiate Phase 1/2 Trial

Steroid Refractory Chronic GVHD

(n ~40)

Data expected in 2019

• Evaluate efficacy, safety and tolerability

• Potential to convert to pivotal trial

Data expected in Q3/Q4 2018

2017 Anticipated Milestones

First Half of 2017:

• Topline data from second Cipro DPI Phase 3 efficacy trial in bronchiectasis (Partner Bayer)

• CHMP opinion regarding conditional market authorization for ONZEALD in Europe (Partner

Daiichi Sankyo)(March)

• Topline data from NKTR-181 Phase 3 efficacy trial in chronic pain (March)

• Initiate first Phase 1 clinical trial in healthy volunteers for NKTR-358 (March)

• Topline data from Amikacin Inhale Phase 3 Program in gram-negative pneumonia (Partner

Bayer)(June-July)

• Potential European approval and launch for ADYNOVATE™ in hemophilia A (Partner Baxalta)

• Data from PIVOT dose-escalation trial (NKTR-214 with Opdivo) in patients with melanoma, non-

small cell lung cancer, and renal cell carcinoma (Ongoing)

Second Half of 2017:

• Continuing data from PIVOT clinical trial of NKTR-214 with Opdivo in patients with melanoma,

non-small cell lung cancer, renal cell carcinoma, triple-negative breast cancer, bladder (Ongoing)

• Data from Phase 1 clinical trial of NKTR-358

• Initiate Phase 1/2 clinical trial of NKTR-358 in lupus and GVHD patients

28

Ended 2016 with $389 Million in Cash & Equivalents

2017 JP Morgan Healthcare Conference Howard W. …€¦ · 2017 JP Morgan Healthcare Conference...

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