Jefferies 2017 Global Healthcare Conference. Stephen Doberstein, Ph.D. Senior Vice President & Chief Scientific Officer

Transcription

1 Jefferies 2017 Global Healthcare Conference Stephen Doberstein, Ph.D. Senior Vice President & Chief Scientific Officer June 7, 2017

2 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-Q filed on May 10, Nektar undertakes no obligation to update forward-looking statements as a result of new information or otherwise.

3 Revenue Potential Building a Biopharmaceutical Growth Company Wholly-Owned Research & Development Pipeline Immuno-Oncology NKTR-214 CD122-biased agonist Multiple Tumor Types Combination Trials NKTR-255 IL-15 NKTR-262 TLR Agonist Revenue Drivers Partnered Portfolio $ M Annual Revenue By 2021 Integrated R&D, Scale-Up and Manufacturing Capabilities R&D Center San Francisco, CA Pain NKTR-181 Abuse-deterrent Opioid NCE Immunology NKTR-358 Autoimmune Disease Manufacturing & Scale-Up Facility Huntsville, AL Cancer Chemotherapy ONZEALD Metastatic Breast Cancer & Brain Metastases 2021 R&D Support Facility Hyderabad, India 3

4 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, dizziness 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 4

5 NKTR-181: Phase 3 Efficacy Trial Conclusions NKTR-181 significantly reduced pain in opioid naïve patients with moderateto-severe chronic low back pain. Primary efficacy analysis: p= Completer efficacy analysis: p< Responder analyses ( 30% and 50% reductions in pain scores) both met statistical significance (p= 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 ( mg) previously demonstrated significantly lower abuse potential than oxycodone (40mg) and rated similar to placebo in a separate Human Abuse Liability (HAL) trial. 5

6 Patients Responding (cumulative) Key Secondary Endpoint: Responder Analysis Based on Pain Scores (NRS) Relative to Screening Baseline 100% p= vs. placebo 90% 80% 71.2% p=0.001 vs. placebo 70% 60% 50% 40% 30% 57.1% 51.1% 37.9% NKTR-181 Placebo 20% 10% 0% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Pain Score Reduction from Screening Baseline Responder 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 6

7 Drug High HAL: Primary Drug High Profile NKTR-181 is Significantly Differentiated from Oxycodone at All Dose Levels (p<0.0001) 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 Emax LS Mean Placebo 8.50 NKTR mg NKTR mg NKTR mg Oxycodone HCl 40mg Study completed May 2013 Pain Med pnw344 (Webster, et al.) March 2017 Time (Hours Post Dose) Link to Manuscript in Pain Medicine 7

8 NKTR-181 Development Strategy Q Q Q Efficacy Study Ongoing in Opioid-naïve Patients with Chronic Low Back Pain Topline Data Announced March 2017 Initiate Partnering Discussions Q Discuss early NDA filing based upon efficacy and HAL trial results 2H 2017 Long-term (52-wk) safety study enrollment complete; 6 & 12-month exposure requirements met Initiate additional trial(s) with Partner to support expansion of label and/or approval Pivotal Human Abuse Liability Study Initiated Topline Data Mid

9 The Immunity Cycle and Multiple Points of Intervention for I-O Therapies 4. Trafficking of T cells to tumor 3. Priming and activation 5. Infiltration of T cells into tumors 2. Cancer antigen presentation 6. Recognition of cancer cells by T cells Source: Oncology Meets Immunology: The Cancer-Immunity Cycle Chen and Mellman Immunity, Volume 39, Issue 1, Release of cancer cell antigens 7. Killing of cancer cells 9

10 Nektar s Immuno-Oncology Strategy to Create Therapies that Cover the Immunity Cycle 4. Trafficking of T cells to tumor (CTLs) NKTR-214 (CD122 Agonist) Target as many steps as possible in the cycle with as few therapies as possible 3. Priming and activation (APCs & T cells) 2. Cancer antigen presentation (dendritic cells/apcs) Prime, Proliferate, Activate & Increase Tumor-Infiltrating Lymphocytes (TILs), Increase PD-1 expression NKTR-262 (TLR Agonist) Activate Dendritic Cell Response 1. Release of cancer cell antigens (cancer cell death) 7. Killing of cancer cells (immune and cancer cells) 5. Infiltration of T cells into tumors (CTLs, endothelial cells) NKTR-255 (IL-15) 6. Recognition of cancer cells by t cells (CTLs, cancer cells) Stimulate NK Cells, Sustain Immune Response & Generate T Cell Memory Therapies need to be accessible as medicines 10

11 NKTR-214 Provides A Central Mechanism to Combine with Multiple Modalities in Immuno-Oncology Checkpoint Inhibitors Vaccines NKTR-214: T Cell Growth Factor Cell Therapies (TIL therapy, ECT) Small Molecules (TLR Agonist, other targets) 11

12 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) NKTR-214 Eliminates overactivation of IL-2 pathway that results in serious safety issues Achieves antibody-like dosing schedule in outpatient setting CTLs CD8+ T-Cells and NK Cells Stimulates Immune Response to Kill Tumor Cells T regs CD4+ Regulatory T-Cells Down-Regulates Proliferation of CD8+ T-cells and Suppresses Immune Response 12

13 NKTR-214 Selectively Grows T Cells, NK Cells in Tumor Microenvironment in Cancer Patients Analysis of T cell Populations in Tumor CD C D Tregs T r e g s 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 Fold change expressed as Week 3 / predose Shown are results from N=10 patients N=10; Q3w dose schedule; SITC 2016; JP Morgan

14 PIVOT Program: NKTR-214 plus Opdivo with Eight Expansion Cohorts Planned PIVOT Phase 1 Dose Escalation (on label indications) N= Melanoma 1 st line PIVOT Expansion Phase 2 Expansion Cohorts 3Q 2017 Melanoma 1 st line, N=28 Melanoma 2 nd line I-O relapsed, N=26 Renal Cell Carcinoma 1 st, 2 nd line I-O naïve NSCLC 1 st, 2 nd line I-O naïve Initial Dose Combination Arm: Group 1: mg/kg q3w NKTR mg q2w nivo q2w and q3w Parallel Dose Combination Arms: Group 2: mg/kg q2w NKTR mg q2w nivo Group 3: mg/kg q2w NKTR mg q2w nivo Group 4: mg/kg q3w NKTR mg q3w nivo Group 5: mg/kg q3w NKTR mg q3w nivo Renal Cell Carcinoma 1 st line, 2 nd line I-O naïve, N=26 Renal Cell Carcinoma 2 nd line I-O relapsed, N=26 NSCLC 1 st, 2 nd line I-O naïve, N=36 NSCLC 2 nd line I-O relapsed, N=26 Urothelial Carcinoma (Bladder) 1 st line, cisplatin ineligible, N=40 Triple Negative BC 2 nd line I-O naïve, N=36 Opdivo is a registered trademark of Bristol-Myers Squibb 14

15 NKTR-214: Additional Clinical Development Programs in 2H 2017/1H 2018 Triplet combination of NKTR-214 with anti-pd-1 and anti-ctla-4 agents Checkpoint Inhibitors Phase 1 trial of NKTR-214 and TECENTRIQ (Q317) IST in Sarcoma with NKTR-214 and Opdivo at Memorial Sloan Kettering and MD Anderson (Q317) TLR Agonist Cell Therapies Phase 1 trial of NKTR-214 and NKTR-262 (TLR Agonist 7/8) Phase 1/2 trial of NKTR-214 in combination with Endogenous T Cell regimen in NSCLC patients (with MDA) Vaccines Preclinical studies underway with NKTR-214 and vaccines with potential for clinical advancement in 2018 Opdivo is a registered trademark of Bristol-Myers Squibb 15

16 Takeda and Nektar Research Collaboration Takeda and Nektar collaborating on combining NKTR-214 with five Takeda oncology compounds Collaboration will explore five targeted mechanisms in 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 16

17 Nektar s Immuno-Oncology Strategy to Create Therapies that Cover the Immunity Cycle 4. Trafficking of T cells to tumor (CTLs) NKTR-214 (CD122 Agonist) Target as many steps as possible in the cycle with as few therapies as possible 3. Priming and activation (APCs & T cells) 2. Cancer antigen presentation (dendritic cells/apcs) Prime, Proliferate, Activate & Increase Tumor-Infiltrating Lymphocytes (TILs), Increase PD-1 NKTR-262 (TLR Agonist) Activate Dendritic Cell Response 1. Release of cancer cell antigens (cancer cell death) expression 7. Killing of cancer cells (immune and cancer cells) 5. Infiltration of T cells into tumors (CTLs, endothelial cells) NKTR-255 (IL-15) 6. Recognition of cancer cells by t cells (CTLs, cancer cells) Stimulate NK Cells, Sustain Immune Response & Generate T Cell Memory Therapies need to be accessible as medicines 17

18 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 microenvironment by mimicking local infection NKTR-262 activates innate immunity M1 Macrophage Dendritic Cell Present antigens to prime T Cell 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-214 proliferates & expands T Cells CD8+ T Cell NKTR-262 with NKTR-214 represent a novel, wholly-owned combination regimen in immuno-oncology 18

19 T u m o r V o l u m e ( m m 3 S E M ) Complete Regression and Abscopal Effect with Combination of NKTR-262 and NKTR-214 T u m o r V o l u m e ( m m 3 S E M ) Primary (injected) CT-26 Colon Tumor Vehicle NKTR-214 NKTR-262 NKTR NKTR D a y s a f t e r f i r s t d o s e Dosing Primary (injected) Tumor NKTR-262 NKTR-214 Secondary (non-injected) Tumor D 0 D 9 D 18 Survival CT-26 Colon Tumor NKTR NKTR-214 Secondary (non-injected) CT-26 Colon Tumor NKTR-214 Vehicle NKTR NKTR-262 NKTR NKTR NKTR Vehicle D a y s a f t e r f i r s t d o s e NKTR mg in 40 μl volume given in a single IT dose, NKTR mg/kg q9dx3 IV; N=10 per group 19

20 Overcomes Immune Suppression Promotes Immune Activation TLR Agonist + NKTR-214: Synergistic Immune Effects on Distal Tumor % T r e g s % M a c r o p h a g e s % M o n o c y te s % C D 1 1 c + C D 8 + D e n d r itic C e lls 7 0 % C D 8 T C e lls % C D 8 T C e lls % C D 1 1 c + C D 8 + D C s V e h ic le N K T R T L R C o m b o % N e u tr o p h ils % N e u tr o p h ils V e h ic le N K T R T L R C o m b o Combination of TLR Agonist + NKTR V e h ic le N K T R T L R C o m b o % T r e g s % M o n o c y te s % M a c r o p h a g e s V e h ic le N K T R T L R C o m b o V e h ic le N K T R T L R C o m b o 0 V e h ic le N K T R T L R C o m b o 20

21 Auto-Immune Disease is Characterized by Imbalance of T-Reg Cells to T-Effector Cells Beneficial effector T cell population Insufficient T-reg cell population to control the pathological effector T cells Pathological overpopulation of antigen-specific (self-reactive) effector T cells 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. 21

22 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? 22

23 NKTR-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 mg/kg single dose SC for NKTR-358 vs QDx5 SC for IL-2. 23

24 P r o te in L e v e l (g /L ) NKTR-358 Suppresses Disease Progression in a Mouse Model of Systemic Lupus Erythematosus 3 Protein Levels in Urine 2 SLE + Vehicle 1 SLE + NKTR-358 Normal Mouse Control N o v D e c D e c D e c D e c J a n J a n J a n J a n F e b F e b F e b F e b -1 7 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. 24

25 NKTR-358: Phase 1/2 Clinical Development H H 2017 Phase 1 Single Ascending Dose Trial in Healthy Subjects Initiate Phase 1b Multiple Ascending Dose Trial in Lupus (SLE) Patients Single SQ Dose of NKTR-358 (n ~50) Multiple SQ Doses of NKTR-358 (n ~50) Evaluate changes in T-reg cells (number) and activation markers (function) Evaluate PK/PD to determine dosing for multiple dose trial Data expected in 2H :1 randomization vs. placebo Evaluate changes in T-reg cells and activation markers Establish P2 doses Data expected in Q3/Q Additional Phase 1/2 trials in other immune disorders are being explored Allergy GVHD Crohn s disease Ulcerative colitis Rheumatoid arthritis Type-1 diabetes Multiple sclerosis Psoriasis 25

26 2H 2017 Anticipated Milestones 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, triplenegative 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