Dinutuximab (ch14.18) for children with high-risk neuroblastoma Malcolm A. Smith, MD, PhD Cancer Therapy Evaluation Program National Cancer Institute November 3, 2015

Neuroblastoma Most common extra-cranial solid tumor in children 700 cases per year in U.S. 90% are younger than 5 years at diagnosis, with a median age at diagnosis of 19 months Approximately 50% have “high risk” features Overall survival for high-risk neuroblastoma < 50%

Dinutuximab (ch14.18) for Children with High Risk Neuroblastoma Over 99% of neuroblastoma expresses GD2 on cell surface Normal tissue expression: tissues of neuroectodermal origin, e.g., skin and nervous system tissue Dinutuximab (ch14.18) binds GD2 and has potent ADCC and CDC activity Matthay & George, Clin Cancer Res. 2012: 8(10):2740-53

Dinutuximab (ch14.18) for Children with High Risk Neuroblastoma Over 99% of neuroblastoma expresses GD2 on cell surface Normal tissue expression: tissues of neuroectodermal origin, e.g., skin and brain tissue Dinutuximab (ch14.18) binds GD2 and has potent ADCC and CDC activity Matthay & George, Clin Cancer Res. 2012: 8(10):2740-53 Matthay & George, Clin Cancer Res. 2012: 8(10):2740-53

Dinutuximab (ch14.18) for Children with High Risk Neuroblastoma Over 99% of neuroblastoma expresses GD2 on cell surface Normal tissue expression: tissues of neuroectodermal origin, e.g., skin and brain tissue Dinutuximab (ch14.18) binds GD2 and has potent ADCC and CDC activity Matthay & George, Clin Cancer Res. 2012: 8(10):2740-53

Dinutuximab (ch14.18) for Children with High Risk Neuroblastoma 1990’s: Phase 1-2 clinical trials 1998: Request to NCI to manufacture agent for phase 3 trial 2001: ANBL0032 activated 2009: Positive results for ANBL0032 identified 2009: ANBL0032 continues as single arm study 2009: ANBL0931 activated 2010: United Therapeutics announced as NCI CRADA partner Children’s Oncology Group

Dinutuximab (ch14.18) for Children with High Risk Neuroblastoma 1990’s: Phase 1-2 clinical trials 1998: Request to NCI to manufacture agent for phase 3 trial 2001: ANBL0032 activated 2009: Positive results for ANBL0032 identified 2009: ANBL0032 continues as single arm study 2009: ANBL0931 activated 2010: United Therapeutics announced as NCI CRADA partner

Dinutuximab (ch14.18) for Children with High Risk Neuroblastoma 1990’s: Phase 1-2 clinical trials 1998: Request to NCI to manufacture agent for phase 3 trial 2001: ANBL0032 activated 2009: Positive results for ANBL0032 identified 2009: ANBL0032 continues as single arm study 2009: ANBL0931 activated 2010: United Therapeutics announced as NCI CRADA partner

Dinutuximab (ch14.18) for Children with High Risk Neuroblastoma 1990’s: Phase 1-2 clinical trials 1998: Request to NCI to manufacture agent for phase 3 trial 2001: ANBL0032 activated 2009: Positive results for ANBL0032 identified 2009: ANBL0032 continues as single arm study 2009: ANBL0931 activated 2010: United Therapeutics announced as NCI CRADA partner ANBL0032 EFS Results (2009) Yu, et al. N Engl J Med. 2010;363:1324-34

Dinutuximab (ch14.18) for Children with High Risk Neuroblastoma 1990’s: Phase 1-2 clinical trials 1998: Request to NCI to manufacture agent for phase 3 trial 2001: ANBL0032 activated 2009: Positive results for ANBL0032 identified 2009: ANBL0032 continues as single arm study 2009: ANBL0931 activated 2010: United Therapeutics announced as NCI CRADA partner March 2015

Public-Private Partnership to Successfully Develop a New Treatment for Children with High-Risk Neuroblastoma NCI UTC COG

Public-Private Partnership to Successfully Develop New Treatments for Children with High-Risk Cancers NCI UTC COG NCI manufacturing (if necessary) of anticancer agent NCI preclinical in vivo testing of clinical candidate Clinical trials through NCI-supported consortia (e.g., COG Phase 1 Consortium) and NCI National Clinical Trials Network Collaboration with pharmaceutical company for commercialization Incentives from Creating Hope Act