Jefferies 2016 Healthcare Conference

Howard Robin

President & Chief Executive Officer

June 8, 2016

This presentation includes forward-looking statements regarding Nektar’s

technology platform, drug candidates, clinical and regulatory objectives, future

availability of clinical trial data, market opportunity estimates, and royalty and

milestone payment 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-K filed on February 29, 2016. Nektar undertakes no

obligation to update forward-looking statements as a result of new

information or otherwise.

Nektar-Owned

Drug

Candidates

3

Partnered

Portfolio

Could Generate

>$750M/year

Royalty Income

Five Mid to Late Stage Clinical Candidates

Two Commercial Products

Three Clinical Drug Candidates

Amikacin Inhale Cipro DPI Fovista® Dapirolizumab pegol

Multiple Candidates Spanning

Immuno-oncology, Immunology and CNS

(Biogen)

PEGPH20

NKTR-181Abuse-deterrent

Opioid NCE

ONZEALD (NKTR-102)Metastatic Breast Cancer with

Brain Metastases

NKTR-214Immuno-Oncology

Nektar Therapeutics: A Broad Portfolio and Pipeline

Next IND Filings/Discovery Programs

NKTR-255Immuno-Oncology

NKTR-358Immunology

The Epidemic of Opioid Abuse and

Addiction

Existing opioid molecules present an intrinsic

abuse and addiction liability

Current opioid formulations can be converted

back to their rapid-acting form by abusers who

seek a “euphoric” high

~26-36 million people abuse opioids

worldwide

Deaths from opioid abuse in U.S. have more

than tripled in the last 20 years

Emergency room visits from opioid overdoses

in U.S. have doubled in the last 5 years

4

All abuse deterrent opioid

formulations are simply pre-cursors

to rapid-acting opioids Oxycodone

Source: Volkow et. al., NIH NIDA 2014 Senate Caucus on International Narcotics Control, “America’s Addiction to Opioids: Heroin and Prescription Drug Abuse”

OxyContin®

NKTR-181: A Novel Opioid Poised to

Transform Treatment of Chronic Pain

NKTR-181 properties are

inherent to molecule and not a

result of a formulation:

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

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

Slow brain entry inherent to molecular structure,

and not a result of a formulation approach

Human Studies Demonstrate that NKTR-181

Enters the Brain Slowly

6

OxycodonePlasma to CNS Equilibration1

NKTR-181Plasma to CNS Equilibration2

2.9 Hours

Pla

sma C

on

cen

trati

on P

up

il Co

nstrictio

n

Plasma Drug

Concentration

Pupil Constriction

11 Minutes

Pla

sma C

on

cen

trati

on P

up

il Co

nstrictio

n

NKTR-181: Phase 2 Human Abuse Liability

Trial

7Abstract #683 / Poster Board #21: Presented at the 2013 College on Problems of Drug Dependence (CPDD) Annual Meeting, San Diego, CA

Time (Hours Post Dose)

Dru

g H

igh

Oral solution:

NKTR-181 has

significantly lower

“drug high” ratings

than oxycodone

(p < 0.0001)

NKTR-181: Phase 3 Efficacy Topline Data in

Q1 2017

First efficacy study ongoing in opioid-naïve patients with

chronic low back pain (SUMMIT-07)

• Topline data expected in Q1 2017

Pivotal human abuse liability study to start in Q4 2016

• Topline data expected in 1H 2017

Second efficacy study planned in opioid-experienced

patients following completion of first efficacy study and

HAL study

Long-term (52-week) safety study (SUMMIT-LTS)

continuing8

ONZEALD™: Collaboration with Daiichi

Sankyo Europe

Topo-I inhibitor targets DNA replication process causing tumor

cell death

ONZEALD (NKTR-102) doubled overall survival in pre-specified

subgroup of patients with breast cancer and brain mets in Phase 3

BEACON trial

CHMP granted accelerated review timeline for ONZEALD

conditional MAA

Collaboration enables potential EU conditional approval and

launch as soon as 2017

Confirmatory trial will enable Nektar to file for ONZEALD approval

in the U.S.

Nektar retains US and ROW rights

Economics:

• Nektar receives $20 million upfront and $10 million for conditional marketing

authorization from EMA

• Nektar receives $25 million for final marketing authorization from EMA with

additional $25 million in potential sales milestones

• Nektar receives 20% royalty on net sales in Europe 9

Goal of Immuno-Oncology is to Optimize

the Immune System to Fight Cancer

10

Generate Tumor Antigen

Radiation, Cytotoxics

Release

Immunosuppression

Checkpoint Inhibitors

Prime, Proliferate,

Activate & Increase

Tumor-Infiltrating

Lymphocytes (TILs)

Sustain Immune

Activation & Boost

Memory

NKTR-214

1

2

3

4

IL-2: A Pathway with Significant Untapped

Potential

IL-2 is the master growth factor for

T-cells and Natural Killer (NK) cells

It was discovered that activation of

IL-2 pathway itself has opposing

effects on the immune response

rhIL-2 protein therapy (aldesleukin)

requires high and frequent dosing in

ICU which results in severe side

effects

11

IL-2: The Central

Immuno-Stimulatory

Cytokine

CTLsb

IL-2 Receptor is an Attractive Cancer Target

but Has Pleiotropic Opposing Effects

12

CD4+ Regulatory T-Cells

Tregs ab

IL-2

Down-Regulates

Proliferation of CD8+ T-cells

and Suppresses Immune

Response

CD8+ T-Cells

and NK Cells

Stimulates Immune

Response to Kill

Tumor Cells

IL-2

IL-2Ra

IL-2RbIL-2R

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

to Stimulate T-Cell Production

13

NKTR-214

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

IL-2RbIL-2R

NKTR-214 Selectively Grows Tumor-killing T Cells

Within the Tumor in B16F10 Mouse Melanoma Model

14

NKTR-214 Single Dose Compared to

to a 15-fold Higher Cumulative Dose

of Aldesleukin

D a y 5 D a y 7

0

1 0 0

2 0 0

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io

D a y 5 D a y 7

0

1 0

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5 0

To

ta

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D8

T c

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s (

%)

B16F10 melanoma, C57Bl/6 mice; N=9-12/group

NKTR-214 2mg/kg i.v. single-dose; Aldesleukin 3mg/kg i.p. BIDx5

NKTR-214 Single Dose:

400-fold Increase in Ratio of CD8+

Tumor-killing T Cells to T-Reg Cells

D a y 5 D a y 7

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V e h i c l e A l d e s l e u k i n N K T R - 2 1 4

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%)

V e h i c l e A l d e s l e u k i n N K T R - 2 1 4

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2 0 0 0

N K T R - 2 1 4

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T u m o r - f r e e

NKTR-214 Produced Complete Responses In

Lewis Lung Carcinoma As Single-Agent

Aggressive model of

squamous lung carcinoma

Therapeutic treatment

(not prophylactic) of

established tumors

15

LLC lung carcinoma, C57Bl/6 mice

NKTR-214, 0.7mg/kg i.v. q9dx3

N=10/group

60% Complete Response

with

Single-Agent NKTR-214

NKTR-214 Produced Survival Benefit as a

Single-Agent in Osteosarcoma

16

Balb/c mice were given K7M2 via IV route.

Arrows, NKTR-214 0.8 mg/kg dosed IV on Days 1, 10, 19 and monitored for survival

K7M2 syngeneic mouse

model of osteosarcoma

• Lung metastasis pathology

NKTR-214 Produced Survival Benefit as a

Single-Agent in Osteosarcoma

17

Balb/c mice were given K7M2 via IV route.

Arrows, NKTR-214 0.8 mg/kg dosed IV on Days 1, 10, 19 and monitored for survival

K7M2 syngeneic mouse

model of osteosarcoma

• Lung metastasis pathology

Only 3 doses of NKTR-214

as a single-agent more than

doubled survival

NKTR-214 dramatically

increased effector cells in

metastasized lung tumors

Establish

Phase 2

Dose

NKTR-214 Single-Agent Phase 1/2 Clinical Trial at

MD Anderson and Yale:Topline Phase 1 Data Expected in 2H 2016

18

One Protocol / Continuous Study

Expansion Cohort 1

Malignant Melanoma

Expansion Cohort 2

Renal Cell

Carcinoma

Expansion Cohort 3

NSCLC

Additional Cohorts

Osteosarcoma/Rare

Tumors

Dose Escalation

• Identify the

recommended

Phase 2 dose

• Safety and

tolerability

• Objective

response rate

(ORR)

• Measure

biomarkers in

blood and tumor

• Enrolling patients

who failed at least

1 prior treatment

regimen

2H 2016

Potential Expansion

Cohorts

N ~ up to 60

Q4 16 - Q1 17

Goal of Immuno-Oncology is to Optimize

the Immune System to Fight Cancer

19

Generate Tumor Antigen

Radiation, Cytotoxics

Release

Immunosuppression

Checkpoint Inhibitors

Prime, Proliferate,

Activate & Increase

Tumor-Infiltrating

Lymphocytes (TILs)

Sustain Immune

Activation & Boost

Memory

NKTR-214

1

2

3

4

NKTR-214: Making Checkpoint Inhibitors

Work Better (Anti-CTLA-4 and Anti-PD-1)

20CT26 colon carcinoma, Balb/c mice; n=10/group

Anti-CTLA-4, 100µg i.p., twice-weekly; Anti-PD-1, 200µg i.p., twice-weekly; NKTR-214, 0.8mg/kg i.v. q9dx3

0 5 1 0 1 5 2 0 2 5 3 0 3 5

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Vehicle

NKTR-214

NKTR-214 + Anti-PD-1

Anti-PD-1

Colon Carcinoma (CT26)

0 5 1 0 1 5 2 0 2 5 3 0 3 5

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(m

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) Vehicle

NKTR-214

Anti-CTLA-4

NKTR-214 + Anti-CTLA-4

NKTR-214: Making Checkpoint Inhibitors

Work Better (Anti-CTLA-4 and Anti-PD-1)

21CT26 colon carcinoma, Balb/c mice; n=10/group

Anti-CTLA-4, 100µg i.p., twice-weekly; Anti-PD-1, 200µg i.p., twice-weekly; NKTR-214, 0.8mg/kg i.v. q9dx3

0 5 1 0 1 5 2 0 2 5 3 0 3 5

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Vehicle

NKTR-214

NKTR-214 + Anti-PD-1

Combination

Anti-PD-1

Colon Carcinoma (CT26)

0 5 1 0 1 5 2 0 2 5 3 0 3 5

0

2 0 0

4 0 0

6 0 0

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D a y s

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(m

m3

) Vehicle

NKTR-214

Anti-CTLA-4

NKTR-214 + Anti-CTLA-4

Combination

Maximal T-cell Expansion and T-Cell Clonality is

Associated with Optimal Anti-Tumor Response

22AACR 2016; Data from Adaptive Biotechnologies; CT26 colon carcinoma, Balb/c mice; n=10/group

Anti-CTLA-4, 100µg i.p., twice-weekly; Anti-PD-1, 200µg i.p., twice-weekly; NKTR-214, 0.8mg/kg i.v. q9dx3

Vehicle

aPD-1

aCTLA-4

NKTR-214

aCTLA4 + aPD-1NKTR-214 + aCTLA4

NKTR-214 + aPD-1

ImmunoSEQ Data in Model of Colon Carcinoma

(in collaboration with Adaptive Biotechnologies)

0 5 1 0 1 5 2 0 2 5 3 0 3 5

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(m

m3

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0 5 1 0 1 5 2 0 2 5 3 0 3 5

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(m

m3

)

NKTR-214 + aPD-1

NKTR-214 + aCTLA4

Goal of Immuno-Oncology is to Optimize

the Immune System to Fight Cancer

23

Generate Tumor Antigen

Radiation, Cytotoxics

Release

Immunosuppression

Checkpoint Inhibitors

Prime, Proliferate,

Activate & Increase

Tumor-Infiltrating

Lymphocytes (TILs)

Sustain Immune

Activation & Boost

Memory

NKTR-214

1

2

3

4

NKTR-255 (IL-15)

ONZEALDTopo-I inhibitor

Auto-Immune Disease is Characterized by

Imbalance of T-Reg Cells to T-Effector Cells

24

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

25

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?

CTLsb

IL-2 Signaling is Required for Regulatory T-Cell

Growth, Survival and Function

26

CD4+ Regulatory T-Cells

Tregs ab

IL-2

Tregs Down-Regulate

Proliferation of CD8+ T-cells

and Suppresses Immune

Response

CD8+ T-Cells

and NK Cells

Stimulates Immune

Response to Kill

Tumor Cells

IL-2

IL-2Ra

IL-2RbIL-2R

NKTR-358: Stimulates Growth of the T-Reg Cell

Population

27

CTLs

CD8+ T-Cells

and NK Cells

b

NKTR-358

Stimulates Immune

Response to Kill

Tumor Cells

CD4+ Regulatory T-Cells

Tregs ab

IL-2RbIL-2R

IL-2Ra

NKTR-358

Tregs Down-Regulate

Proliferation of CD8+ T-cells

and Suppresses Immune

Response

Selectively Expands

T-Reg Cells

NKTR-358 is Selective for Enhancement of T-Reg

Proliferation and Activation in Non-Human Primates

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

281M + 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. Cell analysis conducted using flow cytometry of peripheral blood T cells

Teff

Treg

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

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

Dosing

Fold Change in Treg and Teff

Key Anticipated Milestones

29

Second Half 2016:

• Additional European & rest of world country launches for Movantik™ (Partner

AstraZeneca in ROW and ProStrakan in Europe)

• Topline data from NKTR-214 Phase 1 dose-escalation trial in cancer

• Completion of second Cipro DPI Phase 3 efficacy trial in bronchiectasis (Partner

Bayer)

• Topline data from Fovista™ Phase 3 efficacy trial in wet AMD (Partner Ophthotech)

Q1 2017:

• CHMP opinion regarding conditional market authorization for ONZEALD in Europe

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

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

(Partner Bayer)

• Submit IND filing for NKTR-358

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

Baxalta)