2016 JP Morgan Healthcare Conference. Howard W. Robin President & CEO

Transcription

1 2016 JP Morgan Healthcare Conference Howard W. Robin President & CEO January 12, 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-Q filed on November 6, 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 Wholly-Owned Drug Candidates NKTR-181 Abuse-deterrent Opioid NCE Research Programs NKTR-214 Immuno- Oncology NKTR-102 Metastatic Breast Cancer Multiple Preclinical Drug Candidates Spanning Immuno-oncology, Immunology and CNS 3

4 Movantik : Marketed in U.S. by AstraZeneca & Daiichi Sankyo First and only once-daily oral tablet to treat OIC in patients with chronic, non-cancer pain AstraZeneca & Daiichi Sankyo co-promoting with 1,000+ sales reps in primary care and specialty care Average weekly Total Rx in December ~6,150 with more than 40% of Rx coming from continuing patients* Over 20,000 prescribers with very positive physician and patient reception Over 50,000 new patients started Direct-to-consumer (DTC) campaigns expanding to reach high number of OIC patients As of January 2016, Tier 2 reimbursement now in place for 100% of commercial plans Primary placement for treatment of OIC Royalty rate in U.S. starting at 20% Total sales milestones of $375 million at global annual sales levels *SOURCE: Symphony/Bloomberg (24,667 December Monthly TRx) - Weekly total Rx equals average for December

5 Moventig : Europe and Rest of World Launches Europe Launched in Germany, UK, Ireland, Sweden, Denmark, Norway and Finland NICE issued positive recommendation for Moventig in UK Recently approved in Switzerland Additional European country launches planned for 1H Rest of World Launched in Canada Approved in Australia Filed in South Africa, Argentina and Columbia Royalty rate ex-u.s. starts at 18% 5

6 ADYNOVATE [Antihemophilic Factor (Recombinant)] A Longer-Acting ADVATE for Hemophilia A Baxalta launched ADYNOVATE in U.S. on November 30, 2015 European filing planned for 2016 Full clinical program ongoing to support label expansion in adults and pediatric patients with significant commitment from Baxalta Expands and solidifies Baxalta s leadership position in hemophilia as a longer-acting therapy based upon ADVATE, the gold standard treatment Nektar entitled to receive: Royalties in mid-single digits up to $1.2B Royalties in low teens > $1.2B Up to $55 million in additional development and sales milestones 6

7 Bayer & Nektar Phase 3 Anti-Infective Programs Phase 3 Program Nektar Royalty Cipro DPI Non-Cystic Fibrosis Bronchiectasis (NCFB) Phase 3 RESPIRE program features two 48-week multinational, randomized, placebo-controlled studies in NCFB 10% average (global) Amikacin Inhale Gram-Negative Pneumonia in Ventilated Patients Phase 3 INHALE program features two multinational randomized, placebo-controlled studies in gram-negative pneumonia 30% flat (U.S.) 22% average (ex-u.s.) Phase 3 Data 1H 2016 & 2H 2016 Early 2017 Global Market ~ $750 million* ~ $700 million* Both products granted Qualified Infectious Disease Product (QIDP) Designation from FDA Eligible for fast-track, priority review & 5-year extension of market exclusivity 7

8 The Epidemic of Opioid Abuse and Addiction Existing opioid molecules present an intrinsic abuse and addiction liability Crushing and snorting to increase the euphoric high from existing opioids increase their danger ~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 OxyContin Hydrocodone 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 8

9 NKTR-181: A Novel Opioid Poised to Transform the Chronic Pain Market NKTR-181 brings unique properties to the treatment of chronic pain: $20 Billion+ Global Chronic Pain Therapy Market 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 Antiepileptics $3.6B NSAIDs/COX-2s $5.9B Opioids $12.6B Targeting C-III or better scheduling Properties are inherent to molecule Received Fast Track Status from FDA Chronic pain market includes: Chronic back pain Osteoarthritis Fibromyalgia Neuropathic pain Source: 2013 IMS and Decision Resources 9

10 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 11 Minutes Plasma Drug Concentration Pupil Constriction 2.9 Hours Slow brain entry inherent to molecular structure, and not a result of a formulation approach 10

11 NKTR-181 Achieves Maximum Pupil Constriction Comparable to Oxycodone Pupil constriction is a central effect occurring at the autonomic segment of the oculormotor nerve¹ * Benzinger et al, J Pain Symptom Management, (1997) 13;75; ** Webster et al, Substance Abuse and Rehabilitation, (2012) 3;101; 1. (Lee and Wang 1975; Murray et al. 1983) 11

12 NKTR-181 NKTR-181 Achieves Maximum Pupil Constriction Comparable to Oxycodone NKTR-181 CNS opioid responses are comparable and dose-proportional to those reported for highly efficacious doses of Oxycontin and oxycodone Pupil constriction is a central effect occurring at the autonomic segment of the oculormotor nerve¹ * Benzinger et al, J Pain Symptom Management, (1997) 13;75; ** Webster et al, Substance Abuse and Rehabilitation, (2012) 3;101; 1. (Lee and Wang 1975; Murray et al. 1983) 12

13 NKTR-181: Phase 2 Human Abuse Liability Trial Drug High NKTR-181 has significantly lower drug high ratings than oxycodone Oral solution: (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) 13

14 NKTR-181: Phase 3 Program Underway First efficacy study underway in opioid-naïve patients with chronic low back pain (SUMMIT-07) Topline data expected in 2H 2016 Second efficacy study planned to start in 2H 2016 Trial in opioid-experienced patients with chronic low back pain (SUMMIT-12) after first efficacy completed Long-term (52-week) safety study (SUMMIT-LTS) underway Human abuse liability studies planned to support scheduling and labeling 14

15 Goal of Immuno-Oncology is to Increase Immune Response Against Tumor Checkpoint Control Release brakes on T cells, but need sufficient existing T cells in tumor and creates risk of autoimmunity Tumor Vaccines Increase antigenicity of tumor to induce T cell response, but complexity in antigen selection and dosing Objective: To increase anti-tumor T cell effect Immuno-Stimulatory Cytokine Grow your body s own population of tumor-killing T cells T Cell Therapy Inject tumor-specific T cells into the body, but limited life span and duration of activity 15

16 IL-2: The Central Immuno-Stimulatory Cytokine A Pathway with Huge Untapped Potential Recombinant human IL-2 protein was the first approved immuno-oncology therapy Master growth factor for T-cell and NK-cell activation Has demonstrated complete cures in melanoma and renal cell carcinoma patients However. rhil-2 protein therapy (aldesleukin) required high and frequent dosing which resulted in severe side effects And it was discovered that activation of IL-2 pathway itself has opposing effects on the immune response 16

17 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 17

18 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 18

19 NKTR-214: Molecular Design Fully Captures the Promise of the IL-2 Pathway Biases signaling to favor the IL-2Rβγ complex Eliminates over-activation of IL-2 pathway that results in serious safety issues Provides a sustained and controlled signal to the IL-2 pathway Achieves antibody-like dosing schedule (once every 3 weeks) 19

20 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 ( % ) 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 NKTR-214 Selectively Grows Tumor-killing T Cells Within the Tumor 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 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 20

21 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 21

22 NKTR-214 Single-Agent Phase 1/2 Clinical Trial at MD Anderson and Yale: Topline Phase 1 Data in 2H 2016 One Protocol / Continuous Study Phase 1 Dose Escalation Identify the MTD Expansion Cohort 1 Malignant Melanoma N = up to 60 Safety and tolerability Objective response rate (ORR) Measure biomarkers in blood and tumor Establish Phase 2 Dose Phase 2 NKTR-214 Single-Agent Expansion Cohort 2 Renal Cell Carcinoma N = up to 60 Expansion Cohort 3 NSCLC N = up to 60 Enrolling patients who failed at least 1 prior treatment regimen Additional Cohorts Rare Tumor/Triple Negative Breast N = up to 60 1H H

23 NKTR-214 Provides a Central Mechanism in Immuno-Oncology Making checkpoint inhibitors work better NKTR-214: We Grow T Cells Making vaccines work better Making cell therapies work better (TILs, CAR-T) 23

24 NKTR-214: Making Checkpoint Inhibitors Work Better (Anti-PD1) Breast EMT-6 Carcinoma (Breast)(EMT6) EMT6 mammary carcinoma, Balb/c mice; N=10/group Anti-CTLA-4 100µg i.p., twice-weekly; NKTR mg/kg i.v. q9dx3, Anti-PD-1 200µg i.p., twice-weekly Days 24

25 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 ) 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 Vehicle Anti-CTLA-4 NKTR 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 25

26 NKTR-214: Making Checkpoint Inhibitors Work Better (Anti-PDL-1) Colon Carcinoma (CT26) Aldesleukin Vehicle Anti-PDL-1 Anti-PDL-1 + Aldesleukin NKTR-214 NKTR Anti-PDL-1 CT26 colon carcinoma; Balb/c mice, n=10/group Anti-PDL1, µg i.p., twice-weekly NKTR-214, 0.8mg/kg i.v. q9dx1 colon 26

27 NKTR-214: Making Cell Therapies Work Better Adoptive Cell Therapy (ACT) can stimulate immune response against poorly antigenic tumors Addition of aldesleukin improves ACT response B16F10 Melanoma Model Collaboration with Dr. Antoni Ribas, UCLA ACT Control Arm ACT Aldesleukin C57Bl/6 mouse with B16F10 melanoma tumors ACT from donor pmel mouse splenocytes expanded in vitro NKTR mg/kg q9dx3; aldesleukin 50,000 IU q3d given q9dx3 N=12/group; Research conducted at UCLA through a collaboration with Dr. Antoni Ribas and Dr. Giulia Paris. 27

28 NKTR-214: Making Cell Therapies Work Better B16F10 Melanoma Model Adoptive Cell Therapy (ACT) can stimulate immune response against poorly antigenic tumors Collaboration with Dr. Antoni Ribas, UCLA Addition of aldesleukin improves ACT response Addition of NKTR-214 to ACT therapy more than doubles survival ACT ACT Control Arm Aldesleukin NKTR-214 C57Bl/6 mouse with B16F10 melanoma tumors ACT from donor pmel mouse splenocytes expanded in vitro NKTR mg/kg q9dx3; aldesleukin 50,000 IU q3d given q9dx3 N=12/group; Research conducted at UCLA through a collaboration with Dr. Antoni Ribas and Dr. Giulia Paris. 28

29 NKTR-214: Making Vaccine Therapy Work Better Tumor vaccine therapy can stimulate immune response against poorly antigenic tumors B16F10 Melanoma Model Collaboration with Dr. Overwijk at MD Anderson Cancer Center Addition of aldesleukin improves vaccine therapy response C57Bl/6 mouse B16F10 melanoma tumors, N=5/group Vaccine cocktail (gp100 + anti-cd40 agonist + TLR7 agonist); NKTR mg/kg q9dx3, aldesleukin 100,000 IU BID qdx3 29

30 NKTR-214: Making Vaccine Therapy Work Better Tumor vaccine therapy can stimulate immune response against poorly antigenic tumors B16F10 Melanoma Model Collaboration with Dr. Overwijk at MD Anderson Cancer Center Addition of aldesleukin improves vaccine therapy response Addition of NKTR-214 with vaccine therapy results in 100% survival C57Bl/6 mouse B16F10 melanoma tumors, N=5/group Vaccine cocktail (gp100 + anti-cd40 agonist + TLR7 agonist); NKTR mg/kg q9dx3, aldesleukin 100,000 IU BID qdx3 30

31 NKTR-214 Provides a Central Mechanism in Immuno-Oncology Single-agent efficacy Making checkpoint inhibitors work better NKTR-214: We Grow T Cells Making vaccines work better Making cell therapies work better (TILs, CAR-T) 31

32 Nektar R&D Pipeline Partner Indication Program Preclinical Phase 1 Phase 2 Phase 3 Approved Opioid-Induced Constipation Hemophilia A Chronic Pain Breast Cancer Ventilator Pneumonia Bronchiectasis Neovascular AMD MOVANTIK ADYNOVATE NKTR-181 NKTR-102 Amikacin Inhale Ciprofloxacin DPI FOVISTA (Biogen) IST-High Grade Glioma IST-Small Cell Lung Cancer IST-Non-small Cell Lung Cancer Pancreatic Cancer Immuno-Stimulatory Agent Systemic Lupus Erythematosus Naloxegol + Opioid NKTR-102 NKTR-102 NKTR-102 PEGPH20 NKTR-214 Dapirolizumab pegol NKTR-119 Cancer Immunotherapy Cancer Immunotherapy Cancer Immunotherapy Immunology CNS 32

33 2016 Anticipated Milestones First Half 2016: Topline data from first Cipro DPI Phase 3 efficacy trial in bronchiectasis (Partner Bayer) Additional European & rest of world country launches for Movantik (Partner AstraZeneca) Start of Phase 3 trial for PEG-PH20 in pancreatic cancer (Partner Halozyme ) Second Half 2016: Topline data from NKTR-214 Phase 1 dose-escalation trial in cancer Topline data from NKTR-181 Phase 3 efficacy trial in chronic pain European BLA submission for ADYNOVATE in hemophilia A (Partner Baxalta) Topline data from second Cipro DPI Phase 3 efficacy trial in bronchiectasis (Partner Bayer) Topline data from Fovista Phase 3 efficacy trial in wet AMD (Partner Ophthotech) Early 2017: Topline data from Amikacin Inhale Phase 3 Program in gram-negative pneumonia (Partner Bayer) Ended 2015 with $308.9 Million in Cash & Equivalents 33