Nektar Therapeutics · NASDAQ:NKTR

Nektar Therapeutics — Technical Presentation (November 2011)

22 slides from Nektar Therapeutics's technical presentation, Nov 9, 2011

  1. Slide 1: Final Results of NKTR-102 in Pretreated Metastatic Breast Cancer

    Final Results of NKTR-102 NKTR 102, a Topoisomerase I Inhibitor-Polymer Conjugate, in Patients with Pretreated Metastatic Breast Cancer Demonstrating Significant Antitumor Activity AA Garcia, A Awada, S Chan, G Jerusalem, RE Coleman, M Huizing, A Mehdi, SM O‘Reilly, JT Hamm, PJ Barrett-Lee, V Cocquy

  2. Slide 2: Background

    2 Background g • Worldwide more than 1.6 million women were diagnosed with breast cancer ((BC)) in 20101 — 425,000 deaths in 2010 • In the United States in 20112 — 230,480 230 480 new patients — 39,520 deaths expected • 5-year relative survival varies greatly depending on cancer type, staging and tr

  3. Slide 3: Background: Need For New Therapeutic Options; Irinotecan

    3 Background: Need For New Therapeutic Options; p Irinotecan • Resistance to taxanes and anthracyclines is a significant cause of treatment failure in breast cancer1, 2 — Majority of patients with MBC experience disease progression or recurrence3 — Limiting quality of life and survival • Topoisomera

  4. Slide 4: NKTR-102

    4 NKTR-102 • Topoisomerase I inhibitor(irinotecan)-polymer conjugate • Superior activity compared with irinotecan against a wide range of human xenograft tumors — Measured both by tumor growth delay and regression rate me (mm3) 2000 MCF-7 breast cancer model Doses 1500 umor Volum 1000 Control Irinot

  5. Slide 5: NKTR-102 Mechanism of Action

    NKTR-102 Mechanism of Action The large polymer prodrug does not cross normal vasculature efficiently, limiting concentrations in normal tissues _@, NKTR-102 enters 9% tumor tissue . through leaky » vasculature Hydrolysis of the polymer conjugate releases prodrug Active drug affects tumor cell DNA, i

  6. Slide 6: NKTR-102 Mechanism of Action

    NKTR-102 Mechanism of Action First-generation Topo-I inhibitors have a high initial peak concentration and short half-life 100 Plasma Active 10 Metabolite Concentration (ng/ml) Dose Schedule (weeks)

  7. Slide 7: NKTR-102 Mechanism of Action

    NKTR-102 Mechanism of Action NKTR-102’s design results in a lower initial peak concentration of active Topo [ inhibitor in the blood Active 10 Metabolite Concentration (ng/ml) Dose Schedule (weeks)

  8. Slide 8: NKTR-102 Mechanism of Action

    NKTR-102 Mechanism of Action Due to an extended half life of 50 days, active drug remains in circulation throughout the entire chemotherapy cycle

  9. Slide 9: Study Design: Randomized to Two Schedules

    9 Study y Design: g Randomized to Two Schedules Primary Efficacy Objective: • Determine the objective response rate (ORR) by RECIST v 1.0 10 • Determine the optimal schedule of NKTR-102 in breast cancer Secondary Objectives: PFS PFS, OS and safety Metastatic 145 mg/m2 q14d 145 mg/m2 q14d Primary Bre

  10. Slide 10: Demographics

    10 Demographics g p NKTR-102 NKTR-102 145 mg/m2 145 mg/m2 q14 days q21 days N=35 N=35 Age (years) Median (Range) 53 (33-83) 56 (37-77) ECOG PS 0 15 ((43%)) 13 ((37%)) 1 20 (57%) 22 (63%) Receptor Status* ER+ or PR+ 22 (63%) 21 (60%) ER-/PR-/HER2- (triple negative) 11 (31%) 10 (29%) HER2+ 5 (14%) 1 (

  11. Slide 11: Objective Tumor Response Rate by RECIST

    11 Objective Tumor Response Rate by RECIST ((Investigator g Assessment)) Response by RECIST v 1.0 NKTR-102 NKTR-102 TOTAL 145 mg/m g 2 145 mg/m g 2 q14 days q21 days n 31* 35 66 ORR 10 (32%) 9 (26%) 19 (29%) CR 2 (7%) 0 2 (3%) PR 8 (26%) 9 (26%) 17 (26%) SD 12 (39%) 16 (46%) 28 (42%) PD 9 (29%) 10 (

  12. Slide 12: Response Rate By Prior Therapy

    12 Response p Rate By y Prior Therapy py Prior Therapy Subgroup* Overall Response by RECIST v 1.0 n/N (%) Evaluable Patients NKTR-102 NKTR-102 145 mg/m2 145 mg/m2 TOTAL q14 days q21 days Prior A/T only 7/22 (32%) 5/21 (24%) 12/43 (28%) Prior A/T in MBC 3/7 (43%) 2/9 (22%) 5/16 (31%) P i A/T/C Prior

  13. Slide 13: Maximum Decline in Tumor Measurements

    13 Maximum Decline in Tumor Measurements* 100 6 patients ti t with ith 100% resolution l ti off ttargett llesions i 80 • 2 CRs • 4 near CRs (unresolved non-target lesions) 60 00603: unresolved pleural thickening; bone metastases 02117: unresolved pleural effusion 40 02106: unresolved sclerotic bone

  14. Slide 14: Progression-Free Survival (All Patients)

    14 Progression-Free g Survival ((All Patients)) 1.0000 Median PFS: 0.9000 O Overall: ll 4.6 4 6 months th (95%CI: (95%CI 2.6 2 6 – 5.7) 5 7) q14d: 3.5 months on-free 0.8000 q21d: 5.3 months 0 7000 0.7000 Proportion off Progressio 0.6000 0.5000 0.4000 0.3000 0 2000 0.2000 0.1000 # of Patients 70 41 2

  15. Slide 15: Overall Survival (All Patients)

    15 Overall Survival ((All Patients)) 1.0000 Median OS: 0.9000 O Overall: ll 10.3 10 3 months th (95%CI: (95%CI 8 8.7-15.0) 7 15 0) Q14d: 8.8 months 0.8000 Q21d: 13.1 months Probability of Survivval 0 7000 0.7000 0.6000 0.5000 0.4000 0.3000 0 2000 0.2000 0.1000 # of Patients 70 61 49 42 33 20 6 0 At

  16. Slide 16: Summary of Drug Related Adverse Events

    16 Summary y of Drug g Related Adverse Events 145 mg/m2 145 mg/m2 Most Common Drug-related Grade 3 q14 days* q21 days and 4 Adverse Events > 5% N 35 N=35 N 35 N=35 N (%) Grade 3 Grade 4 Grade 3 Grade 4 Diarrhea 6 (17%) 1 (3%) 8 (23%) 0 Neutropenia 2 (6%) 2 (6%) 3 (9%) 1 (3%) Dehydration 3 (9%) 0 4 (

  17. Slide 17: Time Course of Diarrhea and Neutropenia

    17 Time Course of Diarrhea and Neutropenia p NKTR-102 NKTR-11002 145 mg/m2 q14d 145 mg/m2 q21d N=35 N=35 Diarrhea (≥Grade 3) Cycle 1 and/or 2 9% 3% Cycle 2 and/or 4 0% 6% Cycle 4+ 11% 14% Onset Time, Median (Range) days [# cycle] 88 (1-121) [6] 93 (8-107) [5] Duration, Median (Range) days 8.5 (1-16)

  18. Slide 18: Study Drug Administration and Discontinuation Due to Adverse Event

    18 Study Drug Administration and Discontinuation Due to Adverse Event NKTR-102 145 mg/m2 q14 14 d days** 21 d q21 days TOTAL (N=35) (N=35) (N=70) Discontinuation from Study Drug 7 (20.0%) 5 (14.3%) 12 (17.1%) Due to AE Total Exposure Duration (days) 85 113.5 85 Median (Range) ((1-393)) ((1-420)) ((1

  19. Slide 19: Conclusions

    19 Conclusions • Single-agent NKTR-102 demonstrated a 29% ORR in heavily pretreated advanced breast cancer — PFS: 4.6 months — Preliminary estimate for median OS: 10.3 months • ORR was maintained in heavily pre-treated pre treated and poor prognosis subsets — A/T/C pre-treated: 31% — Triple negative

  20. Slide 20: BEACON Phase 3 Study

    20 BEACON Phase 3 Study NKTR-102 vs. Physician’s y Choice in Women with Metastatic Breast Cancer BrEAst Cancer Outcomes with NKTR-102 Single-agent Primary Endpoint NKTR-102 Overall Survival Q21 day (OS) Metastatic 145 mg/m2 Breast Cancer Patients 1:1 Prior ATC n~840 Physician’s Secondary Choice Endp

  21. Slide 21: Acknowledgements

    21 Acknowledgements g • Investigators and Study Staff at participating centers in the United States, Belgium and United Kingdom: Clatterbridge Centre for Oncology, Bebington, UK; CF Research Resource, East Providence RI; Desert Hematology/Onc, Rancho Mirage, CA; Domaine Universitaire du Sart Tilman,

  22. Slide 22: Thanks! See you in Jacksonville!

    22 Thanks ! See S you in Jacksonville! 26.2 with Donna February 12, 2012 breastcancermarathon.com

Nektar Therapeutics — Technical Presentation (November 2011) on 6ix