18 slides from Kiniksa Pharmaceuticals International's technical presentation, Sep 17, 2018
Slide 1: Acknowledgements and Disclosures
2 Acknowledgments: Study Sponsor: Kiniksa Pharmaceuticals, Ltd. Disclosures: Zamaneh Mikhak, Eben Tessari, Rohan Gandhi, Fang Fang, John F. Paolini: Employees at Kiniksa Pharmaceuticals Corp. Robert Bissonnette: Investigator, Consultant, Advisory Board Member, Speaker for and/or receives honoraria f
Slide 2: KPL-716 simultaneously inhibits both IL-31 and Oncostatin M (OSM) signaling
Pruritus TH2 inflammation Fibrosis Epidermal integrity TH2 inflammation IL-31 TH2 cells sensory neurons keratinocytes KPL-716 OSM Mj T cells PMN mast cell epithelial cells KPL-716 basophils eosinophils mast cell sensory neurons keratinocytes basophils eosinophils mesenchymal lineage cells 3 KPL-716
Slide 3: KPL-716 does not inhibit critical hematopoiesis signaling through OSM/LIFR
KPL-716 does not inhibit critical hematopoiesis signaling through OSM/LIFR Type II OSM Signaling IL-31 Signaling Pruritus TH2 inflammation Fibrosis Epidermal integrity TH2 inflammation IL-31 TH2 cells sensory neurons keratinocytes KPL-716 OSM Mj T cells PMN mast cell epithelial cells KPL-716 basophi
Slide 4: Atopic Dermatitis is a proxy for IL-31-driven pruritic diseases
Atopic Dermatitis (AD) is a proxy for IL-31-driven pruritic diseases 5 1) Raap et al. JACI, 2008; 2) Kim et al. Ann Derm, 2011; 3) Nobbe et al. Acta Derm Venerol, 2012; 4) Bilsborough et al. JACI, 2006; 5) Raap et al. Clin Exp Allergy, 2017; 6) Nemoto et al. BJD, 2016; 7) Ruzicka et al. JEM, 2017; 8
Slide 5: Phase 1a/1b Study Design
KPL-716 Phase 1a/1b Study Design: Double-blind, placebo-controlled, single-ascending-dose 6 Phase 1b: Subjects with AD (n=32) Phase 1a: Healthy volunteers (HV; n=50) Dose Groups 1.5 mg/kg (6 active / 2 placebo) 5 mg/kg (6 active / 2 placebo) 10 mg/kg (6 active / 2 placebo) 20 mg/kg (6 active / 2 pla
Slide 6: Phase 1b: Washout Design, KPL-716 Monotherapy
Phase 1b: Washout Design, KPL-716 Monotherapy 7 Phase 1b: Subjects with AD (n=32) Patient Experience Rescue for flares only SV1 SV2 TCI, Phosphodiesterase inhibitors, anti-histamines prohibited TCS provided to use as needed d0 PK & safety monitoring d28 d60 Entry Criteria: IGA of 3 or 4 >10% BSA WI-
Slide 7: Baseline Parameters were Balanced
Baseline Parameters were Balanced 8 Baseline demographics/disease characteristics: AD KPL-716 7.5 mg/kg IV Placebo Pooled IV Age, mean (SD), years 29.7 (11.2) 41.7 (10.9) Male, % 50 70 White, % 70 70 Elevated IgE, % 60 60 History of any allergic disease, % 40 60 #AD flares in past year, mean (SD) 28
Slide 8: KPL-716 was Well-Tolerated
KPL-716 was Well-Tolerated 9 AE KPL-716 (IV) Placebo (IV) 0.3 mg/kg n=3 1.5 mg/kg n=3 7.5 mg/kg n=10 Pooled n=10 DR-TEAE 0 Mild headache (1), Decreased appetite (1) Moderate dizziness (1) Mild somnolence (1) AD flare 1 0 2 3 Study day of AD flare 7 N/A 14, 20 1, 5, 45 AE KPL-716 (IV) Placebo (IV) 1.
Slide 9: KPL-716 demonstrated dose-dependent elimination (TMDD)
KPL-716 demonstrated dose-dependent elimination (TMDD) 10 TMDD: Target-Mediated Drug Disposition 0.3 1.0 3.0 10.0 30.0 100.0 300.0 1000.0 0 4 8 12 16 Time After Dose (w eeks) C o n c e n t r a t i o n ( m g m L ) 0.3 mg/kg IV 1.5 mg/kg IV 1.5 mg/kg SC 7.5 mg/kg IV
Slide 10: Efficacy Endpoints
Efficacy Endpoints: Pruritus: Weekly average of daily WI-NRS (worst itch in past 24 hours) collected by daily eDiary Pruritus Visual Analog Scale, a component of SCORAD (average itch in past 3 days) collected at study visits Sleep loss VAS: A component of SCORAD (average sleep loss in past 3 nights)
Slide 11: KPL-716 (single dose) reduced pruritus versus Placebo
KPL-716 (single dose) reduced pruritus versus Placebo (28 day monotherapy period) 12 Weekly Average of “Worst Itch Numerical Rating Scale” (WI-NRS) Mean (± SEM) % Change From Baseline (WI-NRS) Weeks Pruritus Visual Analog Scale (VAS)* Weeks Mean (± SEM) % Change From Baseline (Pruritus VAS*) *A comp
Slide 12: KPL-716 (single dose) reduced WI-NRS by >4 Points versus Placebo
KPL-716 (single dose) reduced WI-NRS by >4 Points versus Placebo (28 day monotherapy period) 13 Placebo (Pooled IV) Percentage of Subjects With a >4-Point Reduction in Average Weekly WI-NRS From Baseline Weeks KPL-716 (7.5 mg/kg IV) Subjects, % Subject was considered non-responder after rescue. Two
Slide 13: KPL-716 (single dose) reduced WI-NRS to a greater magnitude versus Placebo
KPL-716 (single dose) reduced WI-NRS to a greater magnitude versus Placebo (28 day monotherapy period) 14 KPL-716 (7.5mg/kg IV) Placebo (Pooled IV) WI-NRS Reduction from Baseline KPL-716 Subjects with >4 WI-NRS Reduction from Baseline Placebo Subjects with >4 WI-NRS Reduction from Baseline 10% 20% 4
Slide 14: KPL-716 (single dose) reduced Sleep Loss versus Placebo
KPL-716 (single dose) reduced Sleep Loss, an important QoL parameter, versus Placebo (28 day monotherapy period) Sleep Loss VAS* *A component of SCORAD. 15 In subjects who received rescue medication, last observation was carried forward. Two KPL-716 recipients (d15, d 21) and three placebo recipient
Slide 15: KPL-716 (single dose) reduced Atopic Dermatitis Disease Severity versus Placebo
KPL-716 (single dose) reduced Atopic Dermatitis Disease Severity versus Placebo (28 day monotherapy period) Mean (± SEM) % Change From Baseline (EASI) Weeks Eczema Area and Severity Index (EASI) 16 Placebo (Pooled IV) KPL-716 (7.5 mg/kg IV) -42.3% -25% In subjects who received rescue medication, las
Slide 16: Summary
First-in-Human, double-blind, placebo-controlled study of KPL-716 met the primary endpoint: KPL-716 was well-tolerated in both healthy volunteers and subjects with AD KPL-716 engaged its target and demonstrated an Early Signal of Efficacy with pruritus reduction Reduction in disease severity (EASI)
Slide 17: Thank You to the Patients, Investigators and Study Staff
Thank You to the Patients, Investigators and Study Staff 18 Joel M. Neutel, MD Orange Country Research Center Tustin, California, USA Robert Bissonnette, MD Innovaderm Montreal, Quebec, Canada Stephen K. Tyring, MD Houston Skin Associates Houston, Texas, USA Thomas Wade, MD QPS-MRA, LLC Miami, Flori
Slide 18: Thank You to the Patients, Investigators and Study Staff
Thank You to the Patients, Investigators and Study Staff Joel M. Neutel, MD Orange Country Research Center Tustin, California, USA Thomas Wade, MD QPS-MRA, LLC Miami, Florida, USA Douglas Denham, DO, CPI Clinical Trials of Texas, Inc. ‘San Antonio, Texas, USA Robert Bissonnette, MD Innovaderm Montre