Nektar Therapeutics · NASDAQ:NKTR
Nektar Therapeutics — Technical Presentation (2019)
22 slides from Nektar Therapeutics's technical presentation, 2019
Slide 1: Phase 1b: Preliminary clinical activity and immune activation for NKTR-262 plus bempegaldesleukin
Phase 1b: Preliminary clinical activity and immune activation for NKTR-262 [TLR 7/8 agonist] plus bempegaldesleukin (NKTR-214) [CD122-biased agonist] in patients (pts) with locally advanced or metastatic solid tumors (REVEAL phase 1b/2 trial) Adi Diab, Mario Marcondes, Fiore Cattaruzza, Brian Kotzin
Slide 2: Presenter Disclosure Information
Presenter Disclosure Information Adi Diab, MD, The University of Texas MD Anderson Cancer Center The following relationships exist related to this presentation: Research funding (institution): Nektar Therapeutics, Bristol-Myers Squibb, Idera Pharmaceuticals, Apexigen, Pfizer Consultation Fees & Advi
Slide 3: NKTR-262 plus Bempegaldesleukin: Targeting the Innate and Adaptive Immune Response
NKTR-262 plus Bempegaldesleukin: Targeting the Innate and Adaptive Immune Response • NKTR-262 is a novel small molecule agonist of toll-like receptors (TLRs) 7/8. NKTR-262 is given by intratumoral injection and designed to be retained in the tumor micro-environment and activate antigen- presenting c
Slide 4: NKTR-262 plus Bempegaldesleukin: Targeting the Innate and Adaptive Immune Response
NKTR-262 plus Bempegaldesleukin: Targeting the Innate and Adaptive Immune Response PRIMING BOOSTING with NKTR-262 with bempegaldesleukin Presented by: Adi Diab 4
Slide 5: REVEAL: NKTR-262 + Bempegaldesleukin Doublet Ongoing Dose-Escalation Portion of Study (Phase 1b)
REVEAL: NKTR-262 + Bempegaldesleukin Doublet Ongoing Dose-Escalation Portion of Study (Phase 1b) Patient Eligibility Criteria for Dose Escalation (Phase 1b): • Patients with locally advanced or metastatic solid tumors and relapsed/refractory to all therapies known to confer any clinical benefit to t
Slide 6: REVEAL Phase 1/2 Study Design to Evaluate Combination of NKTR-262 Plus NKTR-214
REVEAL Phase 1/2 Study Design to Evaluate Combination of NKTR-262 Plus NKTR-214 Melanoma, Merkel Cell, Renal, Urothelial, Triple Negative Breast Cancer, Ovarian, Colorectal, Sarcoma 1&2 3 4+ RP2D – Dose Expansion Dosing Cohorts Same Day Q3W Regimen NKTR-262 Escalating Doses in Combination Doublet wi
Slide 7: Dose Escalation: Patient Disease Characteristics (n=13)
Dose Escalation: Patient Disease Characteristics (n=13) as of January 23, 2019 Dose Escalation Ongoing Cohort 4 q3W Same Day 1 RCC R/R to 1 prior CPI (Doublet) NKTR-262 0.12 mg plus 1 TNBC R/R to 2 prior treatments NKTR-214 0.006 mg/kg 1 RCC R/R to 1 prior CPI* N=3 Cohort 3 1 Mel R/R to 2 Prior CPI
Slide 8: Safety Profile of NKTR-262 and Bempegaldesleukin
Safety Profile of NKTR-262 and Bempegaldesleukin as of January 23, 2019 • Most common treatment-related adverse events (TRAEs) G1-2 were transient flu-like symptoms (69.2%), rash (46.2%), fatigue (46.2%), pruritus (46.2%) and nausea (30.8%) • One patient (7.7%) with Grade 3 TRAEs of maculopapular ra
Slide 9: Plasma Pharmacokinetic Profile Across Escalating Dose Levels of NKTR-262
Plasma Pharmacokinetic Profile Across Escalating Dose Levels of NKTR-262 Mean NKTR-262 Concentration (ng/mL) 0.03, N=3 0.06, N=6 10 0.12, N=3 • Plasma levels of NKTR-262 increased with escalating LLOQ doses • Concentrations of TLR 7/8 agonist resiquimod (R848) released from NKTR-262 were below the l
Slide 10: NKTR-262 and Bempegaldesleukin Promote Comprehensive Activation of the Immune System in the Tumor Microenvironment
NKTR-262 and Bempegaldesleukin Promote Comprehensive Activation of the Immune System in the Tumor Microenvironment REVEAL EXCEL NKTR-262 Monotherapy Bempegaldesleukin Monotherapy 20 20 NKTR-262 IFN-α/β promotes local 10 10 F o ld C h a n g e 5 F o ld C h a n g e 5 Gene (C y c le 1 ) activation of th
Slide 11: Bempegaldesleukin Drives Systemic Proliferation of Lymphocytes to Activate the Adaptive Immune System
Bempegaldesleukin Drives Systemic Proliferation of Lymphocytes to Activate the Adaptive Immune System REVEAL REVEAL 1st Cycle NKTR-262 Alone 2nd Cycle Combination of NKTR-262 + bempegaldesleukin p < 0 .0 0 0 1 100 100 p < 0 .0 0 0 1 p < 0 .0 0 0 1 5 .4 x % K i6 7 + C e lls % K i6 7 + C e lls 80 80 7
Slide 12: Best Overall Response by RECIST 1.1 (Doublet Dose Escalation)
Best Overall Response by RECIST 1.1 as of January 23, 2019 (Doublet Dose Escalation) Totals • 2/5 Stage IV melanoma patients who Total Evaluable* 11 progressed on prior CPI therapies experienced confirmed partial responses ORR (CR+PR) 2 (-100%) and (-50%) CR 0 • 2/2 heavily pre-treated Stage IV PR 2
Slide 13: Case 1: Stage IV Melanoma IO Refractory Confirmed Partial Response (-100%)
Case 1: Stage IV Melanoma IO Refractory Confirmed Partial Response (-100%) • 63-year-old male diagnosed with metastatic melanoma 2/25/17 • Metastatic disease to chest wall (multiple lesions), brain (M1d) • BRAF wild type • Best Response of PD to Prior Cancer Treatment – May 2017 - July 2017: Treated
Slide 14: Case 1: Stage IV Melanoma IO Refractory Confirmed Partial Response (-100%)
Case 1: Stage IV Melanoma IO Refractory Confirmed Partial Response (-100%) Baseline Scan 3 T1 T1 Lesion Description Baseline Scan 1 Scan 2 Scan 3 Exam/Scan Date 2018-04-13 2018-07-02 2018-09-12 2018-10-11 Target Lesions T01: Chest Wall 16 18 11 0 Sum of the diameters (% Change from Baseline) 16 18 (
Slide 15: Case 1: Stage IV Melanoma IO Refractory Confirmed Partial Response (-100%)
Case 1: Stage IV Melanoma IO Refractory Confirmed Partial Response (-100%) • Non-target injected lesions on PET scan showed multiple areas of fibrosis, necrosis and melanophages upon pathology analysis (October 18, 2018) Presented by: Adi Diab 15
Slide 16: Case 2: Stage IV Melanoma IO Refractory Confirmed Partial Response (-50%)
Case 2: Stage IV Melanoma IO Refractory Confirmed Partial Response (-50%) • 71-year-old female diagnosed with metastatic melanoma 2/15/18 • Metastatic disease (M1c) to the lung, adrenal glands, bone, lymph nodes and soft tissue • LDH high, PD-L1 negative at baseline, BRAF wild type • Best Response o
Slide 17: Case 2: Stage IV Melanoma CPI-Refractory Patient Confirmed Partial Response (-50%) with Treatment Ongoing
Case 2: Stage IV Melanoma CPI-Refractory Patient Confirmed Partial Response (-50%) with Treatment Ongoing Lesion Description Baseline Scan 1 Scan 2 Scan 3 Exam/Scan Date 2018-08-29 2018-11-05 2018-12-10 2019-01-07 Target Lesion 1 (T1): Right Anterior Lung 11 4 0 0 Target Lesions Target Lesion 2 (T2)
Slide 18: Case 2: Stage IV Melanoma CPI-Refractory Patient Confirmed Partial Response (-50%) with Treatment Ongoing
Case 2: Stage IV Melanoma CPI-Refractory Patient Confirmed Partial Response (-50%) with Treatment Ongoing Lesion Description Baseline Scan 1 Scan 2 Scan 3 Exam/Scan Date 2018-08-29 2018-11-05 2018-12-10 2019-01-07 Target Lesion 1 (T1): Right Anterior Lung 11 4 0 0 Target Lesions Target Lesion 2 (T2)
Slide 19: Case 2: Stage IV Melanoma CPI-Refractory Patient Confirmed Partial Response (-50%) with Treatment Ongoing
Case 2: Stage IV Melanoma CPI-Refractory Patient Confirmed Partial Response (-50%) with Treatment Ongoing Lesion Description Baseline Scan 1 Scan 2 Scan 3 Exam/Scan Date 2018-08-29 2018-11-05 2018-12-10 2019-01-07 Target Lesion 1 (T1): Right Anterior Lung 11 4 0 0 Target Lesions Target Lesion 2 (T2)
Slide 20: The Combination of NKTR-262 and Bempegaldesleukin Promotes Rapid Clonal Expansion in Blood
The Combination of NKTR-262 and Bempegaldesleukin Promotes Rapid Clonal Expansion in Blood Case Study 2: Stage IV • TCR Repertoire change after a single Melanoma IO Refractory cycle (21 days) of combination treatment – 4/5 patients (80%) had higher clonal expansion Baseline (%) – 4/5 patients (80%)
Slide 21: REVEAL Preliminary Conclusions from Ongoing Dose-Escalation
REVEAL Preliminary Conclusions from Ongoing Dose-Escalation Safety and Tolerability: • NKTR-262 thus far combined with fixed dose of bempegaldesleukin (NKTR-214) was well tolerated • No treatment-related SAEs or DLTs • MTD not reached and dose escalation continuing • NKTR-262 + bempegaldesleukin TRA
Slide 22: Acknowledgements
Acknowledgements A special thank you is extended to the patients, their families and all study staff who are participating and have participated in the REVEAL study MD Anderson Moffitt • Adi Diab, MD • Andrew Brohl, MD Providence Cancer Institute UT Southwestern Medical • Brendan Curti, MD • James B