Nektar Therapeutics · NASDAQ:NKTR
Nektar Therapeutics — Jefferies 2016 Healthcare Conference
29 slides from Nektar Therapeutics's conference presentation, Jun 8, 2016
Slide 1: Jefferies 2016 Healthcare Conference
Jefferies 2016 Healthcare Conference Howard Robin President & Chief Executive Officer June 8, 2016
Slide 2: Forward-looking statements
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 materi
Slide 3: Nektar Therapeutics: A Broad Portfolio and Pipeline
Nektar Therapeutics: A Broad Portfolio and Pipeline Two Commercial Products Partnered Portfolio Could Generate Five Mid to Late Stage Clinical Candidates >$750M/year Royalty Income (Biogen) Amikacin Inhale Cipro DPI Fovista® PEGPH20 Dapirolizumab pegol Three Clinical Drug Candidates NKTR-181 NKTR-21
Slide 4: The Epidemic of Opioid Abuse and Addiction
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
Slide 5: NKTR-181: A Novel Opioid Poised to Transform Treatment of Chronic Pain
NKTR-181: A Novel Opioid Poised to Transform Treatment of Chronic Pain $20 Billion+ NKTR-181 properties are Global Chronic Pain inherent to molecule and not a Therapy Market result of a formulation: Antidepressants Antiepileptics Slow rate of entry into CNS designed $1.5B $3.6B to reduce euphoria
Slide 6: Human Studies Demonstrate that NKTR-181 Enters the Brain Slowly
Human Studies Demonstrate that NKTR-181 Enters the Brain Slowly Oxycodone NKTR-181 Plasma to CNS Equilibration1 Plasma to CNS Equilibration2 Plasma Concentration Plasma Concentration Pupil Constriction Pupil Constriction 2.9 Hours Plasma Drug 11 Minutes Concentration Pupil Constriction Slow brain en
Slide 7: NKTR-181: Phase 2 Human Abuse Liability Trial
NKTR-181: Phase 2 Human Abuse Liability Trial Oral solution: NKTR-181 has significantly lower “drug high” ratings than oxycodone Drug High (p < 0.0001) Time (Hours Post Dose) Abstract #683 / Poster Board #21: Presented at the 2013 College on Problems of Drug Dependence (CPDD) Annual Meeting, San Die
Slide 8: NKTR-181: Phase 3 Efficacy Topline Data in Q1 2017
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 pl
Slide 9: ONZEALD: Collaboration with Daiichi Sankyo Europe
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 revi
Slide 10: Goal of Immuno-Oncology is to Optimize the Immune System to Fight Cancer
Goal of Immuno-Oncology is to Optimize the Immune System to Fight Cancer NKTR-214 2 Prime, Proliferate, Activate & Increase Tumor-Infiltrating Lymphocytes (TILs) 3 Release Generate Tumor Antigen Immunosuppression Radiation, Cytotoxics Checkpoint Inhibitors 1 Sustain Immune Activation & Boost Memory
Slide 11: IL-2: A Pathway with Significant Untapped Potential
IL-2: A Pathway with Significant Untapped Potential IL-2 is the master growth factor for IL-2: The Central T-cells and Natural Killer (NK) cells Immuno-Stimulatory Cytokine It was discovered that activation of IL-2 pathway itself has opposing effects on the immune response rhIL-2 protein thera
Slide 12: IL-2 Receptor is an Attractive Cancer Target but Has Pleiotropic Opposing Effects
IL-2 Receptor is an Attractive Cancer Target but Has Pleiotropic Opposing Effects IL-2R IL-2 IL-2 CTLs Tregs CD8+ T-Cells CD4+ Regulatory T-Cells and NK Cells IL-2R IL-2R Stimulates Immune Down-Regulates Response to Kill Proliferation of CD8+ T-cells Tumor Cells and Suppresses Immune Respo
Slide 13: NKTR-214: Biasing Action to CD122, or IL-2R Beta
NKTR-214: Biasing Action to CD 122, or IL-2R Beta, to Stimulate T-Cell Production NKTR-214 NKTR-214 CTLs Tregs CD8+ T-Cells CD4+ Regulatory T-Cells and NK Cells IL-2R IL-2R Stimulates Immune Down-Regulates Response to Kill Proliferation of CD8+ T-cells Tumor Cells and Suppresses Immune Resp
Slide 14: NKTR-214 Selectively Grows Tumor-killing T Cells in Mouse Melanoma Model
NKTR-214 Selectively Grows Tumor-killing T Cells Within the Tumor in B16F10 Mouse Melanoma Model NKTR-214 Single Dose Compared to NKTR-214 Single Dose: to a 15-fold Higher Cumulative Dose 400-fold Increase in Ratio of CD8+ of Aldesleukin Tumor-killing T Cells to T-Reg Cells 50 Total CD8 / Treg ratio
Slide 15: NKTR-214 Produced Complete Responses In Lewis Lung Carcinoma
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 60% Complete Response with Single-Agent NKTR-214 LLC lung carcinoma, C57Bl/6 mice NKTR-214, 0.7mg/kg i.v. q9dx3
Slide 16: NKTR-214 Produced Survival Benefit as a Single-Agent in Osteosarcoma
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-214 0.8 mg/kg dosed IV on Days 1, 10, 19 and monitored for survival 16
Slide 17: NKTR-214 Produced Survival Benefit as a Single-Agent in Osteosarcoma
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 mi
Slide 18: NKTR-214 Single-Agent Phase 1/2 Clinical Trial at MD Anderson and Yale
NKTR-214 Single-Agent Phase 1/2 Clinical Trial at MD Anderson and Yale: Topline Phase 1 Data Expected in 2H 2016 One Protocol / Continuous Study Potential Expansion Dose Escalation Cohorts N ~ up to 60 • Identify the recommended Phase 2 dose Expansion Cohort 1 Malignant Melanoma • Safety and tolerab
Slide 19: Goal of Immuno-Oncology is to Optimize the Immune System to Fight Cancer
Goal of Immuno-Oncology is to Optimize the Immune System to Fight Cancer NKTR-214 2 Prime, Proliferate, Activate & Increase Tumor-Infiltrating Lymphocytes (TILs) 3 Release Generate Tumor Antigen Immunosuppression Radiation, Cytotoxics Checkpoint Inhibitors 1 Sustain Immune Activation & Boost Memory
Slide 20: NKTR-214: Making Checkpoint Inhibitors Work Better
NKTR-214: Making Checkpoint Inhibitors Work Better (Anti-CTLA-4 and Anti-PD-1) Colon Carcinoma (CT26) NKTR-214 + Anti-CTLA-4 NKTR-214 + Anti-PD-1 1800 1600 1600 1400 Vehicle Vehicle 1400 1200 1200 1000 1000 800 800 Anti-PD-1 Anti-CTLA-4 600 600 NKTR-214 NKTR-214 400 400 200 200 0 0 0 5 10 15 20 25 3
Slide 21: NKTR-214: Making Checkpoint Inhibitors Work Better
NKTR-214: Making Checkpoint Inhibitors Work Better (Anti-CTLA-4 and Anti-PD-1) Colon Carcinoma (CT26) NKTR-214 + Anti-CTLA-4 NKTR-214 + Anti-PD-1 1800 1600 1600 1400 Vehicle Vehicle 1400 1200 1200 1000 1000 800 800 Anti-PD-1 Anti-CTLA-4 600 600 NKTR-214 NKTR-214 400 400 200 200 Combination 0 0 Combi
Slide 22: Maximal T-cell Expansion and Clonality Associated with Optimal Anti-Tumor Response
Maximal T-cell Expansion and T-Cell Clonality is Associated with Optimal Anti-Tumor Response NKTR-214 + aPD-1 ImmunoSEQ Data in Model of Colon Carcinoma (in collaboration with Adaptive Biotechnologies) 1600 1400 1200 1000 800 NKTR-214 + aPD-1 600 400 200 0 0 5 10 15 20 25 30 35 aCTLA4 + aPD-1 Days N
Slide 23: Goal of Immuno-Oncology is to Optimize the Immune System to Fight Cancer
Goal of Immuno-Oncology is to Optimize the Immune System to Fight Cancer 2 NKTR-214 Prime, Proliferate, Activate & Increase ONZEALD Tumor-Infiltrating Topo-I inhibitor Lymphocytes (TILs) 3 Release Generate Tumor Antigen Immunosuppression Radiation, Cytotoxics Checkpoint Inhibitors 1 NKTR-255 (IL-15)
Slide 24: Auto-Immune Disease is Characterized by Imbalance of T-Reg Cells to T-Effector Cells
Auto-Immune Disease is Characterized by Imbalance of T-Reg Cells to T-Effector Cells Pathological Current auto-immune overpopulation of Beneficial antigen-specific disease therapies work by effector T cell population (self-reactive) suppressing overall immune effector T cells system function • Tre
Slide 25: NKTR-358: Growing the Body's Own Population of T-Reg Cells
NKTR-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 25
Slide 26: IL-2 Signaling is Required for Regulatory T-Cell Growth, Survival and Function
IL-2 Signaling is Required for Regulatory T-Cell Growth, Survival and Function IL-2R IL-2 IL-2 CTLs Tregs CD8+ T-Cells CD4+ Regulatory T-Cells and NK Cells IL-2R IL-2R Stimulates Immune Tregs Down-Regulate Response to Kill Proliferation of CD8+ T-cells Tumor Cells and Suppresses Immune Res
Slide 27: NKTR-358: Stimulates Growth of the T-Reg Cell Population
NKTR-358: Stimulates Growth of the T-Reg Cell Population IL-2R NKTR-358 NKTR-358 Selectively Expands T-Reg Cells CTLs Tregs CD8+ T-Cells CD4+ Regulatory T-Cells and NK Cells IL-2R IL-2R Stimulates Immune Tregs Down-Regulate Response to Kill Proliferation of CD8+ T-cells Tumor Cells and Sup
Slide 28: NKTR-358 is Selective for T-Reg Proliferation in Non-Human Primates
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 suppressiv
Slide 29: Key Anticipated Milestones
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 br
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