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Jefferies 2017 Global Healthcare Conference
Stephen Doberstein, Ph.D.Senior Vice President & Chief Scientific Officer
June 7, 2017
This presentation includes forward-looking statements regarding Nektar’sproprietary 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 May 10, 2017. Nektar undertakes no obligation to update forward-looking statements as a result of new information or otherwise.
ONZEALDMetastatic Breast Cancer& Brain Metastases
NKTR-255IL-15
Building a Biopharmaceutical Growth Company
3
Integrated R&D, Scale-Up and Manufacturing
Capabilities
R&D CenterSan Francisco, CA
Manufacturing & Scale-Up FacilityHuntsville, AL
Wholly-Owned Research & Development Pipeline
NKTR-181Abuse-deterrent Opioid NCE
NKTR-214CD122-biased agonistMultiple Tumor TypesCombination Trials
NKTR-358Autoimmune Disease
NKTR-262TLR Agonist
Revenue DriversPartnered Portfolio
$375-450MAnnual Revenue
By 2021Re
venu
e Po
tent
ial
2021
R&D Support FacilityHyderabad, India
Immuno-Oncology
Pain
Immunology
Cancer Chemotherapy
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, dizziness and reduce risk of respiratory depression
Targeting C-III or better scheduling
Properties are inherent to molecule
Received Fast Track Status from FDA
4
$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
OsteoarthritisFibromyalgia
Neuropathic pain
Source: 2013 IMS and Decision Resources
NKTR-181: Phase 3 Efficacy Trial Conclusions
NKTR-181 significantly reduced pain in opioid naïve patients with moderate-to-severe chronic low back pain.
• Primary efficacy analysis: p=0.0019
• Completer efficacy analysis: p<0.0001
Responder analyses (≥30% and ≥50% reductions in pain scores) both met statistical significance (p=0.0003 and p=0.001, respectively).
NKTR-181 improved overall general status and quality of life (p<0.0001).
NKTR-181 improved quality of sleep and led to less sleep disturbance.
NKTR-181 had a favorable safety profile and was well-tolerated.
NKTR-181 dose range evaluated in SUMMIT-07 (100-400mg) previously demonstrated significantly lower abuse potential than oxycodone (40mg) and rated similar to placebo in a separate Human Abuse Liability (HAL) trial.
5
Key Secondary Endpoint:Responder Analysis Based on Pain Scores (NRS) Relative to Screening Baseline
6Responder is defined as a randomized subject who completes the Double-Blind Randomized Treatment Period (Week 12) and achieves ≥30% or ≥50% reduction in the Week 12 Weekly Pain Score from Screening Pain Score
51.1%
71.2%
37.9%
57.1%
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
Pain Score Reduction from Screening Baseline
Patie
nts R
espo
ndin
g (c
umul
ativ
e)
p=0.0003 vs. placebo
NKTR-181
Placebo
p=0.001 vs. placebo
HAL: Primary Drug High ProfileNKTR-181 is Significantly Differentiated from Oxycodone at All Dose Levels (p<0.0001)
7Study completed May 2013Pain Med pnw344 (Webster, et al.) March 2017
Time (Hours Post Dose)
Dru
g H
igh
Oral Human Abuse Liability (HAL)Mean VAS For Drug High
On a scale of 0 to 100,how high do you feel right now?
Treatment EmaxLS Mean
Placebo 8.50
NKTR-181 100mg 14.26
NKTR-181 200mg 14.34
NKTR-181 400mg 22.95
Oxycodone HCl 40mg 80.83
Link to Manuscript in Pain Medicine
NKTR-181 Development Strategy
8
Pivotal Human AbuseLiability Study Initiated
Long-term (52-wk) safety studyenrollment complete; 6 & 12-month
exposure requirements met
Discuss early NDA filing basedupon efficacy and HAL
trial results2H 2017
Initiate additional trial(s) with Partner to support expansion of
label and/or approval
Efficacy Study Ongoing inOpioid-naïve Patients with
Chronic Low Back PainTopline Data Announced
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
9
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 cells1. Release of
cancer cell antigens
2. Cancer antigen presentation
3. Priming and
activation
Source:Oncology Meets Immunology: The Cancer-Immunity CycleChen and MellmanImmunity, Volume 39, Issue 1, 1 - 10
3. Priming and activation
(APCs & T cells)
6. Recognition of cancer cells
by t cells (CTLs, cancer
cells)
5. Infiltration of T cells into tumors (CTLs, endothelial
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)
Nektar’s Immuno-Oncology Strategy to Create Therapies that Cover the Immunity Cycle
10
4. Trafficking of T cells 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
Small Molecules(TLR Agonist,other targets)
NKTR-214 Provides A Central Mechanism to Combine with Multiple Modalities in Immuno-Oncology
11
CheckpointInhibitors
Cell Therapies(TIL therapy, ECT)
VaccinesNKTR-214:
T Cell GrowthFactor
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
12
CTLs
CD8+ T-Cellsand NK Cells
βγ
NKTR-214
Stimulates ImmuneResponse to Kill
Tumor Cells
CD4+ Regulatory T-Cells
Tregs αβγ
Down-Regulates Proliferation of CD8+ T-cells
and Suppresses Immune Response
NKTR-214 Selectively Grows T Cells, NK Cells in 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
13
Fold change expressed as Week 3 / predoseShown are results from N=10 patients
N=10; Q3w dose schedule; SITC 2016; JP Morgan 2016
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
PIVOT Program: NKTR-214 plus Opdivo® withEight Expansion Cohorts Planned
14
Renal Cell Carcinoma1st line, 2nd line I-O naïve, N=26
NSCLC1st, 2nd line I-O naïve
Triple Negative BC2nd line I-O naïve, N=36
Melanoma1st line
Renal Cell Carcinoma1st, 2nd line I-O naïve
Phase 1 Dose Escalation (on label indications)
N= 20-30
Phase 2 Expansion Cohorts3Q 2017
Melanoma2nd line I-O relapsed, N=26
Urothelial Carcinoma (Bladder)1st line, cisplatin ineligible, N=40
Renal Cell Carcinoma2nd line I-O relapsed, N=26
Melanoma1st line, N=28
NSCLC2nd line I-O relapsed, N=26
NSCLC1st, 2nd line I-O naïve, N=36
Initial Dose Combination Arm:Group 1: 0.006 mg/kg q3w NKTR-214 + 240 mg q2w nivoq2w and q3w Parallel Dose Combination Arms:Group 2: 0.003 mg/kg q2w NKTR-214 + 240 mg q2w nivoGroup 3: 0.006 mg/kg q2w NKTR-214 + 240 mg q2w nivoGroup 4: 0.006 mg/kg q3w NKTR-214 + 360 mg q3w nivoGroup 5: 0.009 mg/kg q3w NKTR-214 + 360 mg q3w nivo
PIVOT PIVOT Expansion
Opdivo is a registered trademark of Bristol-Myers Squibb
NKTR-214: Additional Clinical Development Programs in 2H 2017/1H 2018
15
Phase 1 trial of NKTR-214 and TECENTRIQ (Q317)
Phase 1/2 trial of NKTR-214 in combination with Endogenous T Cell regimen in NSCLC patients (with MDA)
Triplet combination of NKTR-214 with anti-PD-1 and anti-CTLA-4 agents
Preclinical studies underway with NKTR-214 and vaccines with potential for clinical advancement in 2018
CheckpointInhibitors
Vaccines
Cell Therapies
Opdivo is a registered trademark of Bristol-Myers Squibb
IST in Sarcoma with NKTR-214 and Opdivo® at Memorial Sloan Kettering and MD Anderson (Q317)
Phase 1 trial of NKTR-214 and NKTR-262 (TLR Agonist 7/8)TLR
Agonist
Takeda and Nektar Research Collaboration
16
Takeda and Nektar collaborating oncombining NKTR-214 with five Takedaoncology compounds
Collaboration will explore five targeted mechanismsin Takeda’s oncology portfolio including:• SYK-inhibitor• Proteasome inhibitor
Combinations will be tested in preclinical models of lymphoma, melanoma and colorectal cancer
Takeda and Nektar will share costs and each will maintain global commercial rights to respective drugs/candidates
3. Priming and activation
(APCs & T cells)
6. Recognition of cancer cells
by t cells (CTLs, cancer
cells)
5. Infiltration of T cells into tumors (CTLs, endothelial
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)
Nektar’s Immuno-Oncology Strategy to Create Therapies that Cover the Immunity Cycle
17
4. Trafficking of T cells 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
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
18
NKTR-214 proliferates &
expands T Cells
NKTR-262 activates
innate immunity
DendriticCell
M1Macrophage
CD8+T Cell
Present antigens to prime T Cell
NKTR-262 0.8 mg in 40 L volume given in a single IT dose, NKTR-214 0.8 mg/kg q9dx3 IV; N=10 per groupμ
Complete Regression and Abscopal Effect with Combination of NKTR-262 and NKTR-214
19
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
TLR Agonist + NKTR-214: Synergistic Immune Effects on Distal Tumor
20
V e h icle
N K T R -21 4
T L R
C o mb o
0
1 0
2 0
3 0
4 0
5 0
% N e u tr o p h ils
% N
eu
tro
ph
ils
V e h icle
N K T R -21 4
T L R
C o mb o
0
1 0
2 0
3 0
4 0
5 0
6 0
7 0
% C D 1 1 c + C D 8 + D e n d r it ic C e lls
% C
D1
1c
+ C
D8
+ D
Cs
V e h icle
N K T R -21 4
T L R
C o mb o
0
1 0
2 0
3 0
4 0
5 0
% C D 8 T C e lls
% C
D8
T C
ell
s
V e h icle
N K T R -21 4
T L R
C o mb o
0
2
4
6
8
1 0
% M o n o c y te s
% M
on
oc
yte
s
V e h icle
N K T R -21 4
T L R
C o mb o
0
1
2
3
4
% T r e g s
% T
reg
s
V e h icle
N K T R -21 4
T L R
C o mb o
0
2 0
4 0
6 0
8 0
% M a c ro p h a g e s
% M
ac
rop
ha
ge
s
Combination of TLR Agonist + NKTR-214
Prom
otes
Imm
une
Activ
atio
nO
verc
omes
Imm
une
Supp
ress
ion
Auto-Immune Disease is Characterized by Imbalance of T-Reg Cells to T-Effector Cells
21
Pathologicaloverpopulation ofantigen-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
22
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-RegProliferation and Activation in Non-Human Primates
23
• 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
TeffTreg
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 Disease Progression in a Mouse Model of Systemic Lupus Erythematosus
24
MRL/MpJ-Faslpr model (N=15/group), NKTR-358 given SC twice weekly at 0.3 mg/kg from Week 8 – 20, beginning on 30Nov2016.Mouse protein levels in urine measured by standard methods. In-life completed on 23Feb2017, additional measures ongoing.
Pro
tein
Le
ve
l (g
/L)
3 0 -No v -1
6
7 -De c -1
6
1 4 -De c -1
6
2 1 -De c -1
6
2 8 -De c -1
6
4 -Ja n -1
7
1 1 -Ja n -1
7
1 8 -Ja n -1
7
2 5 -Ja n -1
7
1 -Fe b -1
7
8 -Fe b -1
7
1 5 -Fe b -1
7
2 2 -Fe b -1
70
1
2
3
SLE + Vehicle
SLE + NKTR-358
Normal Mouse Control
Protein Levels in Urine
NKTR-358: Phase 1/2 Clinical Development
25
H1 2017 2H 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-regcells (number) and activation markers (function)
• Evaluate PK/PD to determine dosing for multiple dose trial
Data expected in 2H 2017
Additional Phase 1/2 trials in other immune disorders are
being explored• Allergy• GVHD• Crohn’s disease• Ulcerative colitis
Data expected in Q3/Q4 2018
• Rheumatoid arthritis• Type-1 diabetes• Multiple sclerosis• Psoriasis
• Dose first patients in Phase 1 PROPEL dose-escalation trial of NKTR-214 in combination with Tecentriq in patients with NSCLC and bladder cancer
• Potential European approval and launch for ADYNOVATE™ in hemophilia A (Partner Shire)
• 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)
• CHMP opinion regarding conditional market authorization for ONZEALD in Europe (Partner Daiichi Sankyo)
• Topline data from Amikacin Inhale Phase 3 Program in gram-negative pneumonia (Partner Bayer)(Q3)
• Data from Phase 1a clinical trial of NKTR-358; initiate potential Phase 1b clinical trial of NKTR-358 in lupus
• File IND for immuno-oncology candidate NKTR-262
2017 Anticipated Milestones
26
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