Jefferies 2016 Healthcare Conference. Howard Robin President & Chief Executive Officer

Transcription

1 Jefferies 2016 Healthcare Conference Howard Robin President & Chief Executive Officer June 8, 2016

2 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, Nektar undertakes no obligation to update forward-looking statements as a result of new information or otherwise.

3 Nektar Therapeutics: A Broad Portfolio and Pipeline Two Commercial Products Partnered Portfolio Could Generate >$750M/year Royalty Income Five Mid to Late Stage Clinical Candidates (Biogen) Amikacin Inhale Cipro DPI Fovista PEGPH20 Dapirolizumab pegol Three Clinical Drug Candidates Nektar-Owned Drug Candidates NKTR-181 Abuse-deterrent Opioid NCE NKTR-214 Immuno- Oncology Next IND Filings/Discovery Programs ONZEALD (NKTR-102) Metastatic Breast Cancer with Brain Metastases NKTR-255 Immuno- Oncology NKTR-358 Immunology Multiple Candidates Spanning Immuno-oncology, Immunology and CNS 3

4 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 Oxycodone OxyContin All abuse deterrent opioid formulations are simply pre-cursors to rapid-acting opioids Source: Volkow et. al., NIH NIDA 2014 Senate Caucus on International Narcotics Control, America s Addiction to Opioids: Heroin and Prescription Drug Abuse 4

5 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 Antidepressants $1.5B $20 Billion+ Global Chronic Pain Therapy Market Antiepileptics $3.6B NSAIDs/COX-2s $5.9B Opioids $12.6B Targeting C-III or better scheduling Received Fast Track Status from FDA Chronic pain market includes: Chronic back pain Osteoarthritis Fibromyalgia Neuropathic pain Source: 2013 IMS and Decision Resources 5

6 Plasma Concentration Human Studies Demonstrate that NKTR-181 Enters the Brain Slowly Plasma Concentration Oxycodone Plasma to CNS Equilibration 1 NKTR-181 Plasma to CNS Equilibration 2 Pupil Constriction Pupil Constriction 2.9 Hours 11 Minutes Plasma Drug Concentration Pupil Constriction Slow brain entry inherent to molecular structure, and not a result of a formulation approach 6

7 NKTR-181: Phase 2 Human Abuse Liability Trial Drug High Oral solution: NKTR-181 has significantly lower drug high ratings than oxycodone (p < ) Abstract #683 / Poster Board #21: Presented at the 2013 College on Problems of Drug Dependence (CPDD) Annual Meeting, San Diego, CA Time (Hours Post Dose) 7

8 NKTR-181: Phase 3 Efficacy Topline Data in Q First efficacy study ongoing in opioid-naïve patients with chronic low back pain (SUMMIT-07) Topline data expected in Q Pivotal human abuse liability study to start in Q 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) continuing 8

9 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

10 Goal of Immuno-Oncology is to Optimize the Immune System to Fight Cancer 2 NKTR-214 Prime, Proliferate, Activate & Increase Tumor-Infiltrating Lymphocytes (TILs) 3 Generate Tumor Antigen Radiation, Cytotoxics Release Immunosuppression Checkpoint Inhibitors 1 Sustain Immune Activation & Boost Memory 4 10

11 IL-2: A Pathway with Significant Untapped Potential IL-2: The Central Immuno-Stimulatory Cytokine 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

12 IL-2 Receptor is an Attractive Cancer Target but Has Pleiotropic Opposing Effects IL-2Ra IL-2 IL-2 b CTLs T regs ab CD8+ T-Cells and NK Cells CD4+ Regulatory T-Cells IL-2R IL-2Rb Stimulates Immune Response to Kill Tumor Cells Down-Regulates Proliferation of CD8+ T-cells and Suppresses Immune Response 12

13 NKTR-214: Biasing Action to CD 122, or IL-2R Beta, to Stimulate T-Cell Production NKTR-214 NKTR-214 b CTLs T regs ab CD8+ T-Cells and NK Cells CD4+ Regulatory T-Cells IL-2R IL-2Rb Stimulates Immune Response to Kill Tumor Cells Down-Regulates Proliferation of CD8+ T-cells and Suppresses Immune Response 13

14 T o t a l C D 8 T c e l l s ( % ) T o t a l C D 8 T c e l l s ( % ) T o t a l C D 8 T c e l l s ( % ) NKTR-214 Selectively Grows Tumor-killing T Cells Within the Tumor in B16F10 Mouse Melanoma Model NKTR-214 Single Dose Compared to to a 15-fold Higher Cumulative Dose of Aldesleukin NKTR-214 Single Dose: 400-fold Increase in Ratio of CD8+ Tumor-killing T Cells to T-Reg Cells T o t a l C D 8 T c e l l s ( % ) T o t a l C D 8 / T r e g r a t i o D ady a5 y D a5 y 5 D ady a7 y D a7 y 7 0 D a y 5 D a y 7 D a y 5 D a y 7 V e Vh ei chv l iec hl ei c l e A l da el ds Al el sd ul ek us i nl ke iun k i n N KNT KR NT - 2R K 1- T24 R B16F10 melanoma, C57Bl/6 mice; N=9-12/group NKTR-214 2mg/kg i.v. single-dose; Aldesleukin 3mg/kg i.p. BIDx5 14

15 NKTR-214 Produced Complete Responses In Lewis Lung Carcinoma As Single-Agent T u m o r V o l u m e ( m m 3 ) N K T R Aggressive model of squamous lung carcinoma Therapeutic treatment (not prophylactic) of established tumors D a y s 6 / 1 0 T u m o r - f r e e 60% Complete Response with Single-Agent NKTR-214 LLC lung carcinoma, C57Bl/6 mice NKTR-214, 0.7mg/kg i.v. q9dx3 N=10/group 15

16 NKTR-214 Produced Survival Benefit as a Single-Agent in Osteosarcoma K7M2 syngeneic mouse model of osteosarcoma Lung metastasis pathology Balb/c mice were given K7M2 via IV route. Arrows, NKTR mg/kg dosed IV on Days 1, 10, 19 and monitored for survival 16

17 NKTR-214 Produced Survival Benefit as a Single-Agent in Osteosarcoma 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 Balb/c mice were given K7M2 via IV route. Arrows, NKTR mg/kg dosed IV on Days 1, 10, 19 and monitored for survival 17

18 NKTR-214 Single-Agent Phase 1/2 Clinical Trial at MD Anderson and Yale: Topline Phase 1 Data Expected in 2H 2016 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 One Protocol / Continuous Study Establish Phase 2 Dose Potential Expansion Cohorts N ~ up to 60 Expansion Cohort 1 Malignant Melanoma Expansion Cohort 2 Renal Cell Carcinoma Expansion Cohort 3 NSCLC Additional Cohorts Osteosarcoma/Rare Tumors 2H 2016 Q Q

19 Goal of Immuno-Oncology is to Optimize the Immune System to Fight Cancer 2 NKTR-214 Prime, Proliferate, Activate & Increase Tumor-Infiltrating Lymphocytes (TILs) 3 Generate Tumor Antigen Radiation, Cytotoxics Release Immunosuppression Checkpoint Inhibitors 1 Sustain Immune Activation & Boost Memory 4 19

20 NKTR-214: Making Checkpoint Inhibitors Work Better (Anti-CTLA-4 and Anti-PD-1) M e a n T u m o r V o l u m e ( m m 3 ) Colon Carcinoma (CT26) NKTR Anti-CTLA-4 NKTR Anti-PD Vehicle Anti-CTLA-4 NKTR-214 M e a n T u m o r V o l u m e ( m m 3 ) Vehicle Anti-PD-1 NKTR D a y s D a y s 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 20

21 NKTR-214: Making Checkpoint Inhibitors Work Better (Anti-CTLA-4 and Anti-PD-1) M e a n T u m o r V o l u m e ( m m 3 ) Colon Carcinoma (CT26) NKTR Anti-CTLA-4 NKTR Anti-PD Vehicle Anti-CTLA-4 NKTR-214 M e a n T u m o r V o l u m e ( m m 3 ) Vehicle Anti-PD-1 NKTR Combination Combination D a y s D a y s 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 21

22 M e a n T u m o r V o l u m e ( m m 3 ) Maximal T-cell Expansion and T-Cell Clonality is Associated with Optimal Anti-Tumor Response M e a n T u m o r V o l u m e ( m m 3 ) NKTR apd-1 ImmunoSEQ Data in Model of Colon Carcinoma (in collaboration with Adaptive Biotechnologies) NKTR apd D a y s NKTR actla4 actla4 + apd-1 NKTR actla4 NKTR Vehicle apd-1 actla D a y s AACR 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 22

23 Goal of Immuno-Oncology is to Optimize the Immune System to Fight Cancer 2 NKTR-214 ONZEALD Topo-I inhibitor Prime, Proliferate, Activate & Increase Tumor-Infiltrating Lymphocytes (TILs) 3 Generate Tumor Antigen Radiation, Cytotoxics Release Immunosuppression Checkpoint Inhibitors 1 NKTR-255 (IL-15) Sustain Immune Activation & Boost Memory 4 23

24 Auto-Immune Disease is Characterized by Imbalance of T-Reg Cells to T-Effector Cells Beneficial effector T cell population Pathological overpopulation of antigen-specific (self-reactive) effector T cells Current auto-immune disease therapies work by suppressing overall immune system function Insufficient T-reg cell population to control the pathological effector T cells Treat symptoms of the overactive immune system Do not address underlying pathology Block both pathological and beneficial effector T cells resulting in infection, bleeding, cancer risks, etc. 24

25 NKTR-358: Growing the Body s Own Population of T-Reg Cells to Treat Auto-Immune Disease 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? 25

26 IL-2 Signaling is Required for Regulatory T-Cell Growth, Survival and Function IL-2Ra IL-2 IL-2 b CTLs T regs ab CD8+ T-Cells and NK Cells CD4+ Regulatory T-Cells IL-2R IL-2Rb Stimulates Immune Response to Kill Tumor Cells Tregs Down-Regulate Proliferation of CD8+ T-cells and Suppresses Immune Response 26

27 NKTR-358: Stimulates Growth of the T-Reg Cell Population IL-2Ra NKTR-358 NKTR-358 Selectively Expands T-Reg Cells b CTLs T regs ab CD8+ T-Cells and NK Cells CD4+ Regulatory T-Cells IL-2R IL-2Rb Stimulates Immune Response to Kill Tumor Cells Tregs Down-Regulate Proliferation of CD8+ T-cells and Suppresses Immune Response 27

28 NKTR-358 is Selective for Enhancement of T-Reg Proliferation and Activation in Non-Human Primates Fold Change in Treg and Teff Treg Teff 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 better approach to treating multiple auto-immune diseases including rheumatoid arthritis, Crohn s disease, psoriasis, lupus, and transplant 1M + 1F cynomolgus monkey per treatment, both agents given at 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 28

29 Key Anticipated Milestones 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) 29