COWEN & COMPANY'S 37TH ANNUAL HEALTHCARE CONFERENCE STEPHEN DOBERSTEIN, PHD SENIOR VICE PRESIDENT & CHIEF SCIENTIFIC OFFICER - MARCH 7, 2017 ...
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Cowen & Company’s
37th Annual Healthcare Conference
Stephen Doberstein, PhD
Senior Vice President & Chief Scientific Officer
March 7, 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-K filed on March 1, 2017. Nektar undertakes no obligation to update forward-looking statements as a result of new information or otherwise.
Building a Biopharmaceutical Growth Company
Wholly-Owned Research & Revenue Drivers Integrated R&D, Scale-Up
Development Pipeline Partnered Portfolio and Manufacturing
Capabilities
Immuno-Oncology
NKTR-214
CD122-biased agonist
Multiple Tumor Types
Combination Trials
$375-450M
NKTR-255 Annual Revenue
IL-15 By 2021 R&D Center
San Francisco, CA
NKTR-262
Revenue Potential
TLR Agonist
Pain
NKTR-181
Abuse-deterrent Opioid NCE Manufacturing & Scale-Up Facility
Huntsville, AL
Immunology
NKTR-358
Autoimmune Disease
Cancer Chemotherapy
ONZEALD R&D Support Facility
Metastatic Breast Cancer Hyderabad, India
& Brain Metastases 2021
3
Revenue from Partnered Programs Supports
Growth of Nektar
$375 - 450M Annual Revenue
By 2021
PEGPH20
(Halozyme)
Amikacin Inhale
(Bayer)
Cipro DPI
(Bayer)
Milestone Potential
Royalty And
Onzeald (EU only)
(Daiichi Sankyo)
(Shire)
(AstraZeneca)
2017 2019 2021
Does not include US revenue for Onzeald. Company estimates, undiscounted.
Adynovate is a registered trademark of Shire plc.
Movantik is a registered trademark of the AstraZeneca group of companies.
4
NKTR-181: A Novel Opioid Poised to Transform
the Chronic Pain Market
$20 Billion+
Global Chronic Pain
NKTR-181 brings unique properties Therapy Market
to the treatment of chronic pain:
Slow rate of entry into CNS designed to Antidepressants Antiepileptics
$1.5B $3.6B
reduce euphoria and resulting abuse
liability
Opioids
Designed to cause less sedation and $12.6B
NSAIDs/COX-2s
reduce risk of respiratory depression $5.9B
Targeting C-III or better scheduling
Properties are inherent to molecule
Chronic pain market includes:
Received Fast Track Status from FDA Chronic back pain
Osteoarthritis
Fibromyalgia
Neuropathic pain
Source: 2013 IMS and Decision Resources 5
NKTR-181 Development Strategy
Q1 2017 Q2 2017 Q3 2017
Initiate Partnering Discuss early NDA filing based
Efficacy Study Ongoing in
Opioid-naïve Patients with Discussions upon efficacy and HAL
trial results
Chronic Low Back Pain Q2 2017
Topline Data 2H 2017
March 2017
Long-term (52-wk) safety study Initiate additional trial(s) with
enrollment complete; 6 & 12-month Partner to support expansion of
exposure requirements met label and/or approval
Topline Data
Mid-2017
Pivotal Human Abuse
Liability Study Initiated
6
The Immunity Cycle and Multiple Points of
Intervention for I-O Therapies
4. Trafficking of
T cells to tumor
3. Priming
and 5. Infiltration
activation of T cells into
tumors
2. Cancer
antigen 6. Recognition
presentation of cancer cells
by T cells
7. Killing of
1. Release of
cancer cells
cancer cell
antigens
Source:
Oncology Meets Immunology: The Cancer-Immunity Cycle
Chen and Mellman
Immunity, Volume 39, Issue 1, 1 - 10 7Nektar’s Immuno-Oncology Strategy to Create
Therapies that Cover the Immunity Cycle
4. Trafficking of T cells
to tumor (CTLs)
3. Priming and
5. Infiltration of T
activation
cells into tumors
Target as (APCs & T cells)
(CTLs, endothelial
cells)
many steps as Therapies
possible in the need to be
cycle with as accessible as
few therapies medicines
as possible 2. Cancer
antigen
presentation 6. Recognition
(dendritic of cancer cells
cells/APCs) by t cells
(CTLs, cancer
cells)
1. Release of cancer 7. Killing of cancer cells
cell antigens (cancer (immune and cancer
cell death) cells)
8Nektar’s Immuno-Oncology Strategy to Create
Therapies that Cover the Immunity Cycle
4. Trafficking of T cells
to tumor (CTLs)
NKTR-214 (CD122 Agonist)
3. Priming and
Prime, Proliferate, Activate &
activation Increase Tumor-Infiltrating 5.cells
Infiltration of T
into tumors
Target as (APCs & T cells)
Lymphocytes (TILs), Increase PD-1 cells)
(CTLs, endothelial
many steps as expression Therapies
possible in the need to be
cycle with as accessible as
few therapies medicines
as possible 2. Cancer
antigen
presentation
NKTR-262
(dendritic
NKTR-255 6.of(IL-15)
Recognition
cancer cells
cells/APCs) by t cells
(TLR Agonist) (CTLs, cancer
cells)
Stimulate NK Cells,
Sustain Immune
Activate Dendritic
Response & Generate
Cell Response
1. Release of cancer 7. Killing of cancer cells
cell antigens (cancer (immune T Cell Memory
and cancer
cell death) cells)
9IL-2 is Master Growth Factor for T Cells and
Natural Killer (NK) Cells
Native IL-2 has
pleiotropic effects on the IL-2
immune response
rhIL-2 protein therapy
(aldesleukin) requires
high and frequent dosing b CTLs Tregs ab
in ICU which results in CD8+ T-Cells CD4+ Regulatory T-Cells
severe side effects and NK Cells
Stimulates Immune Down-Regulates
Response to Kill Proliferation of CD8+ T-cells
Tumor Cells and Suppresses Immune
Response
10NKTR-214: Biasing Action to CD 122, or IL-2R
Beta, to Stimulate T-Cell Production
Biases signaling to favor
the CD122 Receptor (IL- NKTR-214
2Rβγ complex)
Eliminates over-activation
of IL-2 pathway that
results in serious safety b CTLs Tregs ab
issues CD8+ T-Cells CD4+ Regulatory T-Cells
and NK Cells
Achieves antibody-like
dosing schedule in
Stimulates Immune Down-Regulates
outpatient setting Response to Kill Proliferation of CD8+ T-cells
Tumor Cells and Suppresses Immune
Response
11NKTR-214 Selectively Grows T Cells, NK Cells in
Tumor Microenvironment in Cancer Patients
Analysis of T cell Populations in Tumor
NKTR-214 drives immune
activation in the tumor
• Increase in total T cells, NK
440
and CD8 T cells
0
29.8 • No increase in Tregs
330
0
• Increase in PD-1 positive CD8
T cells
220
0
• Increase in newly proliferating
CD8 T cells
110
0
• Activation and expression of
1.6
anti-tumor genes
00
CD8
C D 8 Tregs
T re g s • Change in T cell clonality in
the tumor
Fold change expressed as Week 3 / predose
Shown are results from N=10 patients
12BMS and Nektar Clinical Collaboration for
NKTR-214 and Opdivo®
• 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
Opdivo is a registered trademark of Bristol-Myers Squibb 13PIVOT Program: NKTR-214 plus Opdivo® with
Eight Expansion Cohorts Planned
PIVOT-02 PIVOT-04
Phase 1 Dose Escalation Phase 2 Expansion Cohorts
(on label indications) Q2 2017
N= 30-40
Melanoma
1st line, N=28
Melanoma
1st line Melanoma
2nd line I-O relapsed, N=26
Renal Cell Carcinoma
Renal Cell Carcinoma 2nd line I-O naïve, N=26
2nd line I-O naïve Renal Cell Carcinoma
2nd line I-O relapsed, N=26
NSCLC
NSCLC 2nd line I-O naïve, N=36
2nd line I-O naïve NSCLC New
Indication
2nd line I-O relapsed, N=26
Initial Dose Combination Arm: Urothelial Carcinoma (Bladder)
Group 1: 0.006 q3w NKTR-214 + 240 mg q2w nivo
q2w and q3w Parallel Dose Combination Arms: 1st line, cisplatin ineligible, N=44
Group 2: 0.003 q2w NKTR-214 + 240 mg q2w nivo
Group 3: 0.006 q2w NKTR-214 + 240 mg q2w nivo
Triple Negative BC
Group 4: 0.003 q3w NKTR-214 + 360 mg q3w nivo 2nd line I-O naïve, N= 36
Group 5: 0.006 q3w NKTR-214 + 360 mg q3w nivo
Group 6: 0.009 q3w NKTR-214 + 360 mg q3w nivo (optional) Opdivo is a registered trademark of Bristol-Myers Squibb 14NKTR-214 Provides A Central Mechanism to Combine
with Multiple Modalities in Immuno-Oncology
Checkpoint
Inhibitors
Vaccines Cell Therapies
(TIL therapy, ECT)
NKTR-214:
T Cell Growth
Factor
Small Molecules
(TLR Agonist,
other targets) 15PROPEL Program: NKTR-214 plus
TECENTRIQ® (atezolizumab)
PROPEL
Phase 1 Dose Escalation NKTR-214 in combination
(on label indications)
N= 20-30 with Roche’s anti-PD-L1
agent, atezolizumab
NSCLC
2nd line – metastatic disease
with progression following Nektar sponsored program
platinum regimen or EGFR or
targeted therapy
supporting checkpoint
inhibitor combination
Urothelial Carcinoma strategy
2nd line locally advanced or
metastatic disease with Study is expected to initiate
progression following
platinum regimen mid-2017
16NKTR-214: Additional Development Programs
in 2017
Initiate triplet combination trial of NKTR-214 with anti-PD-1
and anti-CTLA-4 agents
Checkpoint
Inhibitors Initiate IST in Sarcoma with NKTR-214 and Opdivo® at
Memorial Sloan Kettering and MD Anderson
Initiate Phase 1 trial of NKTR-214 and TECENTRIQ
Cell Therapies Initiate Phase 1/2 trial of NKTR-214 in combination with
(TIL therapy, ECT)
Endogenous T Cell regimen in non-small cell lung cancer
patients expressing the MAGE-A3 antigen (with MD
Anderson)
Vaccines Preclinical studies underway with NKTR-214 and therapeutic
tumor vaccines with potential for clinical advancement in
2017
17
Opdivo is a registered trademark of Bristol-Myers SquibbNektar’s Immuno-Oncology Strategy to Create
Therapies That Cover the Immunity Cycle
4. Trafficking of T cells
NKTR-214 (CD122 Agonist) to tumor (CTLs)
Prime, Proliferate, Activate &
3. Priming and
activation Increase Tumor-Infiltrating 5.cells
Infiltration of T
into tumors
Target as Lymphocytes (TILs), Increase PD-1
(APCs & T cells)
(CTLs, endothelial
cells)
many steps as expression Therapies
possible in the need to be
cycle with as accessible as
few therapies medicines
as possible 2. Cancer
antigen
presentation
NKTR-262
(dendritic
NKTR-2556.of(IL-15)
Recognition
cancer cells
cells/APCs) by t cells
(TLR Agonist) (CTLs, cancer
cells)
Stimulate NK Cells,
Sustain Immune
Activate Dendritic
Response & Generate
Cell Response
1. Release of cancer 7. Killing of cancer cells
cell antigens (cancer (immune T Cell Memory
and cancer
cell death) cells)
18NKTR-255: Stimulates Memory T Cell and NK
Cell Activation
IL-15 delivers T-cell survival
signal, promotes CD8 memory
cell formation and activates NKTR-255 is first
Natural Killer (NK) cells with potential medicine to
minimal CD4 activity access the IL-15
• Short half-life of native IL-15 pathway by
requires high and frequent dosing
with prohibitive side effects preserving receptor
binding to IL-15Ra
NKTR-255 designed to
with antibody-like
overcome native IL-15
shortcomings dosing
19NKTR-255 Induces Sustained Signaling and Cell
Proliferation In Vivo
IL-15 NKTR-255
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.
Source: Poster #342 presented at SITC 2016, National Harbor, Maryland 20Nektar’s Immuno-Oncology Strategy to Create
Therapies that Cover the Immunity Cycle
4. Trafficking of T cells
NKTR-214 (CD122 Agonist) to tumor (CTLs)
Prime, Proliferate, Activate &
3. Priming and
activation Increase Tumor-Infiltrating 5.cells
Infiltration of T
into tumors
Target as Lymphocytes (TILs), Increase PD-1
(APCs & T cells)
(CTLs, endothelial
cells)
many steps as expression Therapies
possible in the need to be
cycle with as accessible as
few therapies medicines
as possible 2. Cancer
antigen
presentation
NKTR-262
(dendritic
NKTR-2556.of(IL-15)
Recognition
cancer cells
cells/APCs) by t cells
(TLR Agonist) (CTLs, cancer
cells)
Stimulate NK Cells,
Sustain Immune
Activate Dendritic
Response & Generate
Cell Response
1. Release of cancer 7. Killing of cancer cells
cell antigens (cancer (immune T Cell Memory
and cancer
cell death) cells)
21NKTR-262: Adding a Unique Intratumoral TLR
Agonist to Nektar’s Immuno-Oncology Portfolio
M1 Dendritic
TLR agonists activate innate Macrophage Cell
immunity, myeloid cell response and
increase tumor antigen presentation
NKTR-262
• Creates tumor-suppressing micro- activates
environment by mimicking local innate Present antigens
infection immunity to prime T Cell
Nektar technology optimizes CD8+
specific abscopal effect in tumors T Cell
without systemic exposure of TLR
agonist
NKTR-214
NKTR-262 designed to be highly proliferates &
synergistic with NKTR-214 expands T Cells
NKTR-262 with NKTR-214 represent
a novel, wholly-owned combination
regimen in immuno-oncology
22Complete Regression and Abscopal Effect with
Combination of NKTR-262 and NKTR-214
Primary (injected) CT-26 Colon Tumor Dosing
Primary (injected) Tumor
1000
SEM )
NKTR-262
Vehicle
NKTR-214
3
T u m o r V o lu m e (m m
500 Secondary (non-injected) Tumor D0 D9 D 18
NKTR-214
NKTR-262
NKTR-262 + NKTR-214 Survival CT-26 Colon Tumor
0
0 10 20 30 40 50
NKTR-262 + NKTR-214
D a y s a f te r fir s t d o s e
Secondary (non-injected) CT-26 Colon Tumor
1000
NKTR-214
Vehicle
SEM )
3
NKTR-214
T u m o r V o lu m e (m m
500
NKTR-262
NKTR-262
Vehicle
NKTR-262 + NKTR-214
0
0 10 20 30 40 50
D a y s a f te r fir s t d o s e
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 23Overcomes Immune Promotes Immune
Suppression Activation
% T re g s % C D 8 T C e lls
0
1
2
3
4
0
10
20
30
40
50
V V
e e
h h
ic ic
le le
N N
K K
T T
R R
-2 -2
1 1
4 4
T T
L L
R R
% T re g s
C C
o
% C D 8 T C e lls
m o
b m
o b
o
% C D11c+ C D8+ D C s
0
10
20
30
40
50
60
70
% M a c ro p h a g e s
V
e
0
20
40
60
80
h
ic
V le
e
h
ic
le N
K
T
N R
K -2
T 1
R 4
-2
1
4
Effects on Distal Tumor
T
L
R
T
L
R
C
o
m
C b
o o
m
% M a c ro p h a g e s
b
o
Combination of
% C D 1 1 c + C D 8 + D e n d r it ic C e lls
TLR Agonist + NKTR-214
% M o n o c y te s % N e u t r o p h ils
0
2
4
6
8
10
0
10
20
30
40
50
V V
e e
h h
ic ic
le le
N N
K K
T T
R R
-2 -2
1 1
4 4
T T
L L
R R
C C
% M o n o c y te s
% N e u t r o p h ils
o o
m m
b b
o o
TLR Agonist + NKTR-214: Synergistic Immune
24Auto-Immune Disease is Characterized by
Imbalance of T-Reg Cells to T-Effector Cells
• Current auto-immune
disease therapies work
Pathological
overpopulation of
by suppressing overall
Beneficial
effector T cell
antigen-specific immune system function
(self-reactive)
population
effector T cells
– Treat symptoms of the
over-active immune
system
– Do not address
Insufficient
T-reg cell
underlying pathology
population to – Block both pathological
control the and beneficial effector T
pathological
effector T cells cells resulting in
infection, bleeding,
cancer risks, etc.
25NKTR-358: Growing the Body’s Own Population
of T-Reg Cells to Treat Auto-Immune Disease
What if you could grow the
body’s own population of T-
reg cells and directly treat
the underlying disease
pathology?
Restore balance
and normalize
T-reg cell and T-
effector cell
function
26NKTR-358 is Selective for Enhancing of T-Reg
Proliferation and Activation in Non-Human Primates
Fold Change in Treg and Teff T-Reg Activation Markers
Treg
Teff
Dosing Dosing
• 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
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. 27NKTR-358 Suppresses Antigen-Driven Inflammation
in Preclinical Model of Cutaneous Hypersensitivity
Sensitization (KLH flank) Elicitation in ear (with KLH)
Measure ear swelling
Day 0 Day 5
Cutaneous Hypersensitivity Response
16
(m m , m e a n S E M )
14
12
V e h ic le
10
N K T R - 3 5 8 , 0 .0 0 3 m g / k g
8
N K T R - 3 5 8 , 0 .0 1 m g / k g
e a r th ic k n e s s
6 N K T R - 3 5 8 , 0 .0 3 m g / k g
N K T R - 3 5 8 , 0 .1 m g / k g
4
C y c lo s p o r in A , 1 0 m g / k g
2 N K T R - 3 5 8 , 0 .3 m g / k g
0
0 24 48 72 96
T im e a f t e r K L H c h a lle n g e (h )
Dosing begun on Day 0: NKTR-358, SC q3d, Cyclosporin A, PO qd N=10 28NKTR-358 Suppresses Disease Progression in a
Mouse Model of Systemic Lupus Erythematosus
3 Protein Levels in Urine
SLE + Vehicle
P r o t e in L e v e l ( g /L )
2
1
SLE + NKTR-358
Normal Mouse Control
0
7
7
7
7
7
7
6
6
6
6
7
7
6
-1
-1
-1
-1
-1
-1
-1
-1
-1
-1
-1
-1
-1
n
n
n
n
c
c
c
v
b
b
c
b
b
a
a
a
a
e
e
e
o
e
e
e
e
e
-J
-J
-J
-J
-D
-D
-D
-F
-F
-D
-F
-F
-N
1
8
5
4
5
2
1
8
4
1
8
7
0
1
1
2
1
2
1
2
2
3
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.
29NKTR-358: Phase 1 Clinical Development in
Systemic Lupus Erythematosis
Q1-Q3 2017 Q3 2017
Phase 1 Initiate Phase 1b
Single Ascending Dose Trial in Multiple Ascending Dose Trial in
Healthy Subjects Lupus (SLE) Patients
Single SQ Dose of NKTR-358 Multiple SQ Doses of NKTR-358
(n ~50) (n ~50)
• 3:1 randomization vs. placebo
• Evaluate changes in T-reg • Evaluate changes in T-reg cells
cells (number) and activation and activation markers
• Establish P2 doses
markers (function)
Data expected in Q3/Q4 2018
• Evaluate PK/PD to determine
dosing for multiple dose trial Additional Phase 1/2 trials
in other immune disorders are
Data expected in Q3 2017 being explored
• Allergy • Rheumatoid arthritis
• GVHD • Type-1 diabetes
• Crohn’s disease • Multiple sclerosis
• Ulcerative colitis • Psoriasis
302017 Anticipated Milestones
First Half of 2017:
• Topline data from second Cipro DPI Phase 3 efficacy trial in bronchiectasis (Partner Bayer)
• 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)
• CHMP opinion regarding conditional market authorization for ONZEALD in Europe (Partner Daiichi Sankyo)(Q2)
• 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 Shire)
• Data from PIVOT dose-escalation trial (NKTR-214 with Opdivo) in patients with melanoma, non-small cell lung
cancer, and renal cell carcinoma (June)
Second Half of 2017:
• Dose first patients in Phase 1 PROPEL dose-escalation trial of NKTR-214 in combination with Tecentriq in patients
with NSCLC and bladder cancer
• 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 1a clinical trial of NKTR-358
• Initiate Phase 1b clinical trial of NKTR-358 in lupus
• File IND for immuno-oncology candidate NKTR-262
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