Slide 1: Naloxegol: an investigational drug for the treatment of Opioid-Induced Constipation
Naloxegol an investigational drug for the treatment of Opioid-Induced Constipation October 2012
Slide 2: Cautionary Statement Regarding Forward-Looking Statements
Cautionary Statement Regarding F Forward-Looking d L ki Statements St t t In order, among other things, to utilise the 'safe harbour' provisions of the US Private Securities Litigation Reform Act 1995, we are providing the following cautionary statement: This presentation contains certain forward fo
Slide 3: Introduction and Overview
Introduction and Overview Section Speaker p Introduction Kathy Cantagallo naloxegol VP, Development Overview of the Opioid Market Mike Gibbs VP Brand Marketing g Naloxegol: Overview of the Mark Sostek, M.D. molecule and its development Executive Director, Development Overview and Summary Kathy Canta
Slide 4: Introduction Key Facts
Introduction Key Facts AstraZeneca and Nektar Therapeutics entered into an exclusive 1 worldwide license agreement for naloxegol on 21 September 2009. 2009 AstraZeneca has development and commercialization rights for naloxegol (previously NKTR-118). Nektar received an upfront payment of $125m. $125m
Slide 5: Opioid Market Overview
Opioid Market Overview
Slide 6: Worldwide total opioid sales and volume
Worldwide total opioid sales and volume* Sales Standard Units ($mil) (mil) $15,000 39,500 $14,500 38,500 $14,000 37,500 $13 500 $13,500 $13,000 36,500 $12,500 35,500 MAT MAT MAT MAT MAT MAT MAT MAT MAT MAT Q2/08 Q2/09 Q2/10 Q2/11 Q2/12 Q2/08 Q2/09 Q2/10 Q2/11 Q2/12 Approximately 85% of opioid volume
Slide 7: The opioid market is dominated by US, Canada, France, Germany and UK
The opioid market is dominated by US, Canada, France, Germany and UK* Sales Standard Units ($mil) (mil) ALL ALL OTHER OTHER 19 5% 19.5% JAPAN 21 0% 21.0% JAPAN 0.4% 3.3% U. S. CANADA 49.3% CANADA 4.8% 4.4% U. S. 54.3% 54 3% FRANCE 4.8% FRANCE 5.1% UK UK 5.4% 14.0% GERMANY 8.4% GERMANY N = $14.8 bn 5
Slide 8: Opioid Induced Constipation
Opioid Induced Constipation Mechanism of Opioid-Induced Constipation Although highly effective in the control of pain, the use of opioids is associated with a Opioids bind to μ-opioid receptors in GI tract key side effect - constipation1 – affecting 40-50% of patients.2 GI motility, secretion, fluid
Slide 9: The Opioid Induced Constipation (OIC) opportunity
The Opioid Induced Constipation (OIC) opportunity Of the $14.8 billion global opioid market, five markets $14.8 account for ~80% of total unit volume: US (49%), UK (14%), Germany (5%), Canada (5), France (5%).1 PCPs and Billion Pain Management g Specialists p prescribers in these markets. 2 comprise
Slide 10: Competitive landscape for OIC
Competitive landscape for OIC Peripherally Acting mu-Opioid Receptor Antagonists: RELISTOR (methylnaltrexone bromide) SQ - Salix/Progenics • Indicated for OIC in patients with advanced medical illness who are receiving palliative care care, when response to laxative therapy has not been sufficient •
Slide 11: OIC from a Customer Perspective: Patients, Physicians, Payers
OIC from a Customer Perspective: Patients, Physicians, Payers 11 Source: Patient quotes are from qualitative interviews with US OIC patients, August 2012. HCP quotes are from qualitative interviews with US HCPs, October 2009.; Payor quote from qualitative interviews with US payors, January 2012.
Slide 12: Naloxegol: An overview of the molecule and development
Naloxegol An overview of the molecule and development
Slide 13: Naloxegol Mechanism of Action
Naloxegol M h i Mechanism off Action A ti • Opioids bind to mu-opioid receptors located throughout the body (including b i and brain d gut) t)1 • When opioids bind to mu-opioid receptors in the brain the outcome is p pain relief1 • When opioids bind to mu-opioid receptors in the GI tract/gut the out
Slide 14: NKTR-118: Phase II Study 07-IN-NX003 Design
NKTR-118: Phase II Study 07-IN-NX003 Design ~10 Days 14 Days 7 Days 28 Days 14 ±2 Days Single-Blind Double-Blind Placebo Run-In Active Initial OIC Screening Screening (<3 SBMs/wk) Follow-Up Single-Blind Double-Blind Placebo Run-In Placebo Randomization Daily oral dosing for 28 days 5, 25, and 50 mg
Slide 15: Summary of Patient Demographics and Disposition (Phase II Study)
Summary of Patient Demographics and Disposition p (Phase ( II Study) y) 5 mg QD 25 mg QD 50 mg QD Total Randomized R d i d Pbo NKTR- Pbo NKTR- Pbo NKTR- 118 118 118 N = 208 (N=36) (N=35) (N=29) (N=31) (N=39) (N=37) N=207 g Age (years) Mean 48.0 50.5 51.2 51.8 48.7 51.4 50.2 (SD) (12.2) (12.7) (12.8)
Slide 16: Phase II Study: Primary Efficacy Endpoint
Phase II Study Primary Efficacy Endpoint: Change from Baseline in Spontaneous Bowel Movements (SBMs/week) Week 1 of Double Blind Treatment P = NS P = 0.002 P = 0.0001 5 4 nge in SBM (SE) 4.4 5 mg: 4.4 SBM/week 25 mg: 5.0 SBM/week 3 3.6 50 mg: 6.0 SBM/week 2 Significant over 4-wk 4 wk Chan 2.6 1.9 1.
Slide 17: Phase II Study: Median Time to First Spontaneous Bowel Movement
Phase II Study Median Time (hrs) to First Spontaneous Bowel Movements NS P = 0.001 P < 0.002 60 hrs) to Fiirst SBM M 50 48.6 44.9 40 28.2 Placebo 30 Naloxegol (NKTR-118) Time (h 20 10 6.2 6.6 29 2.9 0 5 mg 25 mg 50 mg Webster et al. Am J Gastroenterol 2009; 104 ( Suppl 3) : S 466 P-values based on a
Slide 18: Safety: Most Common Adverse Events (Phase II)
Safety: Most Common Adverse Events ( Phase II) (>10%, any grade) 5 mg QD 25 mg QD 50 mg QD % of Patients Placebo NKTR-118 Placebo NKTR-118 Placebo NKTR-118 Reporting at (N=32) (N=33) (N=27) (N=30) (N=37) (N=35) Least 1 Adverse Event Abdominal Pain 3 3 7 30 0 17 Nausea 3 15 19 13 8 20 Diarrhea 16 15
Slide 19: Summary of Key Outcomes in Phase II study
Summary of Key Outcomes in Phase II study • Primary Endpoint • Statistically Significant difference versus placebo for 25 and 50 mg doses in change from Baseline in Spontaneous Bowel Movements (SBM) at week 1 • Secondary Safety Endpoints - Patient Pain Assesment • No statistically significant differ
Slide 20: Naloxegol core KODIAC Phase III Clinical Program
Naloxegol core KODIAC Phase III Clinical Program 2011 2012 2013 2014 2015 PH3 ID KODIAC 4 (Pivotal) St d Countries Study C ti US KODIAC 7 (DBE) H2 EU Australia KODIAC 5 (Pivotal) PLANNED SUBMISSION KODIAC 8 (LTS) Primary Endpoint - Percentage of responders over 12 weeks (Responder: >3 SBMs/week with
Slide 21: Phase III (Study 4 and 5) Design
Phase III (Study 4 and 5) Design 5 to 14 Days 14 Days 12 Weeks 14 Days Double-Blind Active 12.5 mg (Visits 3 to 8) Initial Screening OIC Confirmation Double-Blind Active Follow-up (Visit 1) (Visit 2) 25 mg (Visit 9) (Visits 3 to 8) Double-Blind Placebo (Visits 3 to 8) Randomization (Visit 3) N= 210/
Slide 22: Phase III Long Term Safety Study (8) Design
Phase III Long Term Safety Study (8) Design Randomization 52-week treatment period Patients from study 25 mg QD open-label D3820C00005 or study D3820C00007 can be randomized without a 2-week follow-up period screening period or an OIC confirmation period Usual Care OIC therapy (Physician’s (Physicia
Slide 23: Naloxegol Key Facts
Naloxegol Key Facts
Slide 24: Summary Key Facts
Summary y Key y Facts • Naloxegol is a once a day oral, peripherally acting, μ-opioid receptor antagonist under investigation for the treatment of Opioid-Induced Constipation (OIC). • OIC may occur when h opioids i id bi bindd tto opioid i id receptors t iin gastrointestinal t i t ti l tract causing
Slide 25: Summary Key Facts
Summary Key Facts • Global opioid market: • Of the $14.8 billion global opioid market, five markets account for ~80% of total unit volume: US (49%), UK (14%), Germany (5%), Canada (5), France (5%). • In these five markets there are 69 million patients taking opioids for chronic pain (>30 days treatm
Slide 26: Naloxegol Q&A
Naloxegol Q&A