Piper Jaffray 29 th Annual Healthcare Conference

Transcription

1 Piper Jaffray 29 th Annual Healthcare Conference Jonathan Zalevsky, Ph.D. Senior Vice President, Research and Chief Scientific Officer November 28, 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 November 8, Nektar undertakes no obligation to update forwardlooking statements as a result of new information or otherwise. ASCO 2017

3 Building a Biopharmaceutical Growth Company Partner Indication Program Preclinical Phase 1 Phase 2 Phase 3 Approved Opioid-Induced Constipation Hemophilia A U.S. Hemophilia A - Europe MOVANTIK ADYNOVATE ADYNOVI Positive CHMP Opinion Chronic Pain NKTR-181 (Partner in EU Only) (Biogen) Breast Cancer with Brain Mets Pancreatic Cancer Systemic Lupus Erythematosus ONZEALD PEGPH20 Dapirolizumab pegol Cancer Immunotherapy Cancer Immunotherapy Immunology Cancer Immunotherapy Cancer Immunotherapy Cancer Immunotherapy NKTR OPDIVO NKTR TECENTRIQ or KEYTRUDA NKTR-358 NKTR NKTR-214 NKTR-255 (IL-15) NKTR-262 (TLR Agonist) Clinical collaboration ASCO

4 NKTR-181: A Novel Opioid Poised to Transform the Chronic Pain Market NKTR-181 brings unique properties to the treatment of chronic pain: 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 Targeting C-III or better scheduling Properties are inherent to molecule Received Fast Track Status from FDA Source: 2013 IMS and Decision Resources Antidepressants $1.5B $20 Billion+ Global Chronic Pain Therapy Market Antiepileptics $3.6B NSAIDs/COX-2s $5.9B Opioids $12.6B Chronic pain market includes: Chronic back pain Osteoarthritis Fibromyalgia Neuropathic pain ASCO

5 NKTR-181: Positive Phase 3 Efficacy Trial NKTR-181 Met All Primary & Secondary Endpoints 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. ASCO

6 Primary Endpoint Drug Liking NKTR mg & 600 mg Dose Comparison to Oxycodone Strong Liking (=100) Mean Drug Liking Bipolar VAS (mm) Oxy 60 mg Oxy 40 mg NKTR mg NKTR mg and 600 mg had a significantly lower rating of peak (Emax) liking compared to both doses of oxycodone NKTR mg p< (all comparisons) Treatment Emax (LS Mean) Placebo 53.2 NKTR mg 62.0* NKTR mg 67.9 Oxycodone 40 mg 76.6 Oxycodone 60 mg 81.5 Neutral (=50) Placebo Strong Disliking (=0) Time (Hours Post Dose) ASCO 2017 *The peak liking score for NKTR mg oral tablet confirmed the same peak liking score for NKTR mg oral solution evaluated in the company s prior HAP study (62.0 vs 62.3**). ** Webster et al.; Human Abuse Potential of the New Opioid Analgesic Molecule NKTR-181 Compared with Oxycodone. Pain Med 2017 pnw344. doi: /pm/pnw344 6

7 CNS Dopamine Release in Preclinical Studies Shows Marked Difference to Oxycodone Dopam ine Release in Aw ake Rat 200 Dopam ine (% of basal levels at 0 m in) 150 Vehicle O xycodone 1 m g/kg NKTR m g/kg 100 Therapeutic Dose NKTR T im e (m in ) Mean, N=6/group ASCO

8 NKTR-181: NDA Submission & Timeline Pre-NDA meeting request granted; meeting scheduled in Q NDA submission planned with large clinical data package: 600-patient efficacy study in patients with chronic pain who are new to opioid therapy 630-patient long-term 52-week safety and efficacy trial PK and PD studies in over 450 healthy subjects (therapeutic and supratherapeutic NKTR-181 studies) Human abuse potential study of therapeutic and supratherapeutic NKTR- 181 doses in recreational drug users (tablets) Human abuse potential study of therapeutic NKTR-181 doses in recreational drug users (solution) Completion of stability studies on final drug product will support NDA submission in April 2018 ASCO

9 Nektar s Growing IO Pipeline Targeting the Innate and Adaptive Immune System Discovery and Development Clinical Combination Announced Clinical Trials Large Molecules NKTR-214 (CD122-biased agonist) NKTR-255 (Memory T cell/nk cell stimulator ) Small Molecules NKTR-262 (TLR 7/8 agonist) NKTR Checkpoint Inhibitors Small molecules Vaccines Cell therapies NKTR NKTR-214 NKTR-255 (Preclinical) + NK cells CAR-T ASCO

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

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) ASCO

12 NKTR-214 Selectively Grows T Cells, NK Cells in Tumor Microenvironment in Cancer Patients Analysis of T cell Populations in Tumor 0 CD CD8 1.6 Tregs s Fold change expressed as Week 3 / predose Shown are results from N=10 patients N=10; Q3w dose schedule; SITC 2016; JP Morgan 2016 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 ASCO

13 NKTR-214 Broad Clinical Development Program NKTR Nivolumab Melanoma (IO-naive, IO R/R) RCC (IO-naive, IO R/R) NKTR Atezolizumab Bladder cancer NSCLC NKTR NKTR-214 Melanoma R/R RCC R/R TNBC NSCLC (IO-naive, IO R/R) Bladder cancer NKTR Pembrolizumab Melanoma NSCLC Ovarian Cancer Colorectal Cancer Merkel Cell Carcinoma R/R TNBC Bladder cancer Bladder Cancer R/R ASCO

14 PIVOT-02 Study: NKTR Nivolumab Dose Escalation Phase Confirmed locally advanced or metastatic solid tumors Measurable disease per RECIST 1.1 ECOG 0 or 1 Patients IO Treatment-Naïve MEL 1L (with known BRAF status) (N=11) RCC 1L, 2L (N=22) NSCLC 1L, 2L (EGFR & ALK WT) (N=5) Adequate organ function Fresh biopsy and archival tissue Phase 1b (N=38) NKTR mg/kg Q3W + NIVO 240 mg Q2W N=4 NKTR mg/kg Q2W + NIVO 240 mg Q2W N=3 NKTR mg/kg Q2W + NIVO 240 mg Q2W NKTR mg/kg Q3W + NIVO 360 mg Q3W N=3 N=3 RP2D NKTR mg/kg Q3W + NIVO 360 mg Q3W MAD NKTR mg/kg Q3W + NIVO 360 mg Q3W Dose Limiting Toxicities (N=2) N=22 N=3 ASCO

15 NKTR Nivolumab Shows Tumor Reduction for Both PD-L1 Negative and Positive Patients Best % Change in Tumor Size from Baseline 26/36 (72%) Reduction in Target Lesions 32/36 (89%) Disease Control Rate Tumor Histology * Best overall response is PD (SD for target lesions, PD per non-target lesions) # Best overall response is SD (PR for target lesions, PD per new lesion at confirmatory scan) + Best overall response is PR (CR for target lesions, non-target lesions still present) Data are shown for patients with post-baseline scans that included assessment of target lesions. Two patients not included in the figure: one patient discontinued from study due to clinical progression before the first post-baseline tumor assessment and one patient on treatment does not have a post-baseline scan. ASCO

16 Stage IV Treatment-Naïve Melanoma Patients (N=11) Best Overall Response by RECIST: ORR*=7/11 (64%); DCR=10/11 (91%) Best Overall Response by irrecist: ORR=8/11 (73%); DCR=10/11 (91%) % Change From Baseline in Target Lesions % Change in Target Lesions Over Time Best % Change in Tumor Size from Baseline Change in Tumor Size (%) from Baseline Median TTR 1.7 mos Weeks Since Treatment Initiation Horizontal dotted lines indicate the thresholds for PD and response according to RECIST (version 1.1) criteria. # Best Overall Response is SD (PR for target lesions, PD per new lesion on confirmatory scan) + Best Overall response is PR (CR for target lesions, non-target lesions still present), *One patient in ORR calculation has unconfirmed PR. ASCO

17 Stage IV Treatment-Naïve 1L Renal Cell Carcinoma (N=13) Efficacy-evaluable patients with 1 or 2 post baseline scans Best ORR by RECIST 1 post baseline scan: ORR=6/13 (46%); DCR=11/13 (85%) % Change From Baseline in Target Lesions % Change in Target Lesions Over Time Best % Change in Tumor Size from Baseline PD-L1 Negative Change in Tumor Size (%) from Baseline Median TTR 1.9 mos Weeks Since Treatment Initiation Horizontal dotted lines indicate the thresholds for PD and response according to RECIST (version 1.1) criteria. * Best overall response is PD (SD for target lesions, PD per non-target lesions). ASCO

18 Stage IV Treatment-Naïve 1L Renal Cell Carcinoma (N=13) Efficacy-evaluable patients with 1 or 2 post baseline scans Best ORR by RECIST 1 post baseline scan: ORR=6/13 (46%); DCR=11/13 (85%) Best ORR by RECIST 2 post baseline scans: ORR=6/10 (60%); DCR=8/10 (80%) % Change From Baseline in Target Lesions % Change in Target Lesions Over Time Best % Change in Tumor Size from Baseline PD-L1 Negative Change in Tumor Size (%) from Baseline 2 Scans 1 ucr 5 PR 2 SD 2 PD ** Median TTR 1.9 mos Weeks Since Treatment Initiation Horizontal dotted lines indicate the thresholds for PD and response according to RECIST (version 1.1) criteria. * Best overall response is PD (SD for target lesions, PD per non-target lesions). ** Includes PD with 1 post base-line scan ASCO

19 NSCLC: Minimal Clinical Benefit in Patients with PD-L1 <1% Nivo 3 Q2W + Ipi 1 Q2/12W (pooled) Nivo 3 Q2W ORR% Combination and single agent perform identically Overall PD-L1 50% PD-L1 25% PD-L1 10% PD-L1 5% PD-L1 1% PD-L1 <1% n PD-L1 Expression Source: Checkmate-012; Presented By Matthew Hellmann at 2016 ASCO Annual Meeting ASCO

20 Stage IV IO-Naïve PD-L1 Negative NSCLC (1L and 2L) Best Overall Response by RECIST (2L): ORR=3/4 (75%); DCR=3/4 (75%) Best Overall Response by RECIST (1L and 2L): ORR=3/5 (60%); DCR=3/5 (60%) % Change From Baseline in Target Lesions % Change in Target Lesions Over Time Best % Change in Tumor Size from Baseline 1L Change in Tumor Size (%) from Baseline Median TTR (2L) 1.7 mos Weeks Since Treatment Initiation Horizontal dotted lines indicate the thresholds for PD and response according to RECIST (version 1.1) criteria. ASCO

21 PIVOT-02 Dose Expansion Underway in 13 Cohorts MEL 1L MEL 2/3L IO naïve IO R/R Phase 2 (N= ~330) N= per cohort RP2D RCC 1L RCC 2/3L IO naïve IO R/R NSCLC 1L PD-L1 50% NSCLC 1L PD-L1 <1% NKTR mg/kg Q3W + NIVO 360 mg Q3W NSCLC 1L IO naïve NSCLC 1L PD-L1 1% to <50% N=22 NSCLC 2L NSCLC 2/3L IO naïve IO R/R NSCLC 2L PD-L1 <1% UC 1L UC (Bladder) 1L UC (Bladder) 2/3L IO naïve IO R/R UC 1L Cisplatin-ineligible TNBC 1/2L IO naïve R/R: Progressed on Anti-PD-(L)1 ASCO

22 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 ASCO

23 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 ASCO

24 NKTR-262: Adding a Unique Intratumoral TLR Agonist to Nektar s Immuno-Oncology Portfolio TLR agonists activate innate immunity, myeloid cells and increase tumor antigen presentation NKTR-262 designed with Nektar technology to be highly synergistic with NKTR-214 NKTR-262 with NKTR-214 represents a novel, wholly-owned combination regimen in IO ASCO

25 Tumor Regressions and Abscopal Effect from NKTR NKTR-214 EMT6 (Bilateral) CT26 (Bilateral) Mammary Carcinoma Colon Carcinoma Tumor Volume (mm 3 ± SEM) % CR Tumor Volume (mm 3 ± SEM) Treated tumors: Vehicle NKTR-262 NKTR-214 NKTR NKTR-214 Abscopal tumors: Vehicle NKTR-262 NKTR-214 NKTR NKTR % CR D ays after treatm ent start D ays after treatm ent start ASCO

26 Lilly and Nektar: Strategic Development & Commercialization Collaboration for NKTR-358 Nektar will receive initial payment of $150M and up to $250M in additional development and regulatory milestones Lilly and Nektar will co-develop NKTR-358 with Nektar responsible for completing Phase 1 clinical development Lilly and Nektar will share Phase 2 development costs 75% Lilly and 25% Nektar Nektar to participate in Phase 3 development on an indicationby-indication basis with the opportunity to receive double-digit royalties up to the low twenties Lilly is responsible for all costs of global commercialization Nektar has an option to co-promote in the U.S. under certain conditions ASCO

27 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. ASCO

28 Piper Jaffray 29 th Annual Healthcare Conference Jonathan Zalevsky, Ph.D. Senior Vice President, Research and Chief Scientific Officer November 28, 2017