SIR ABSTRACT #1 Safety, Response and Survival Outcomes of Y90 Microsphere Radioembolization for Liver Metastases: Results from a 151 Patient Investigational Device Exemption Multi- Institutional Study Study Chair – Dr. Al Benson III, Northwestern Memorial Hospital Principle Investigators – Dr. Gary Siskin, Albany Medical Center – Dr. Jeff Geschwind, Johns Hopkins University Hospital – Dr. Gregory Wiseman, Mayo Clinic Rochester – Dr. William Rilling, Medical College of Wisconsin – Dr. Mary Mulcahy, Dr. Riad Salem, Northwestern Memorial Hospital

TheraSphere Y-90 integral constituent of the insoluble, biocompatible glass microspheres Mean sphere diameter :  m 22,000 to 73,000 spheres / mg 6 dose sizes (3, 5, 7, 10, 15, 20 GBq) Dose by selected target volume Activity = [Desired Dose (Gy)] [Mass of Liver Target (kg)] 50 Arterial administration preferentially delivers microspheres to tumor; spares normal parenchyma Comparison of a Human Hair with TheraSphere  (500x) TheraSphere Y-90 Glass microspheres Radiation

Study Overview Design Single-arm prospective, open-label Investigational Device Exemption (Nordion) Independent contract research organization Patients with Liver Metastases: – Primary Colorectal Cancer (CRC) – Neuroendocrine (NE) – Non-Colorectal/Non-Neuroendocrine (Non-CRC/Non-NE) Objectives Evaluate safety of TheraSphere at doses of 120 ± 10% Gy Evaluate Imaging Outcomes (RECIST v1.0) – Response Rate (RR) – Progression Free Survival (PFS) – Independent central review Evaluate Overall Survival (OS)

Main Inclusion Criteria ≥ 18 years of age Metastatic disease refractory to, or inappropriate for other systemic or liver-directed therapies Unresectable tumors Measurable disease Tumor replacement  50% by liver volume ECOG PS 0-2 ≥ 30 day from prior cancer therapy Signed informed consent

Main Exclusion Criteria Risk of hepatic or renal failure – Serum creatinine >2.0 mg/dL, unless on dialysis – Serum bilirubin  2.0 mg/dL – Albumin < 2.0 g/dL – History of hepatic encephalopathy Pulmonary insufficiency, clinically evident COPD Contraindication to TheraSphere or radiology procedures Cirrhosis or portal hypertension Prior Y90 microspheres or EBRT to the liver Intervention for, or compromise of the Ampulla of Vater Clinically evident ascites Co-morbidities or unresolved adverse events Positive serum pregnancy test

Trial Treatment Schedule Pre-Treatment Procedures (< 28 days prior to Day 0) – Screening for eligibility, informed consent; medical history; labs; CT/MRI; 99 TcMAA scan and hepatic angiography (coil embolization) – Develop treatment plan: determine target volume; activity to treat target volume; account for decay; schedule treatment, order dose vial Day 0 - Treatment first lobe: position catheter, infuse microspheres Week 2 – Telephone follow-up (safety) Week 5 – Assess safety & response, treat 2 nd lobe Months 3, 6, 9, 12 then every 6 months – Assess safety & progression

Study Enrollment First patient enrolled: January 2007 Last patient enrolled: October 2009 Last patient visit: by March 1, 2011 Study Center CRC N=61 NE N = 44 Non CRC / Non NE N = 46 All Patients N = 151 N (%) Albany Medical Center 17 ( 27.9)5 ( 11.4)10 ( 21.7)32 ( 21.2) Johns Hopkins12 ( 19.7)11 ( 25.0)4 ( 8.7)27 ( 17.9) Mayo Clinic4 ( 6.6)10 ( 22.7)8 ( 17.4)22 ( 14.6) Medical College Wisconsin 8 ( 13.1)8 ( 18.2)6 ( 13.0)22 ( 14.6) Northwestern University 20 ( 32.8)10 ( 22.7)18 ( 39.1)48 ( 31.8)

Results – Patient Population Mean age 63.7 years 55.6 % male 91.4 % Caucasian 95.4 % ECOG % bilobar disease Mean 2.5 years from initial diagnosis Medical history consistent with age/disease: – > 50% patients with histories in GI, Musculoskeletal, General Cardiac, Dermatology, Allergy/immunology & Endocrine body systems Non CRC/Non NE included: cholangiocarcinoma, breast, ovarian, renal cell/bladder, esophageal/gastric, lung, pancreas

Results – Prior Treatments Prior Therapy CRC N = 61 NE N = 44 Non CRC/ Non-NE N = 46 All Patients N = or fewer therapies43%93%59%62% 3 or more therapies57 %7%41%38% Systemic Chemotherapy100%30%70% Hormone Therapy0%50%20% Other30%10%20%

Results – Dosing 243 lobar treatments per protocol Average 1.6 treatments per patient All patients received 120 Gy +/ – 20% – No USNRC reportable medical events Median cumulative lung exposure <10 Gy 2% of patients received > 30 Gy to lung without clinical sequelae

Results – Total Liver Dosing (Gy) CRC N = 61 NE N = 44 Non CRC/ Non- NE N = 46 All Patients N = 151 Mean (SD)115.3 ( 7.62)116.4 ( 7.79)116.3 ( 7.11)116.0 ( 7.48) Median (IQR)114.3 ( 11.4)115.0 ( 9.3)116.1 ( 9.0)115.0 ( 10.3) Min, Max100, , 13897, 13397, 138 Site 1Site 2Site 3Site 4Site 5 Mean (SD) ( 5.93)116.3 ( 5.39)117.3 ( 5.48)120.2 ( 8.39)111.7 ( 5.92) Median (IQR) ( 7.1)117.4 ( 6.7)116.7 ( 8.3)119.6 ( 11.1)110.7 ( 7.9) Min, Max 102, , , 12697, , 130

Study Analysis Populations Safety and OS populations all patients receiving TheraSphere (N = 151) RR (CR+PR+SD) patients with completed independent image review (N = 130) PFS populations CRC patients (N = 56), NE patients (N = 31) with complete independent image review

Response by RECIST v1.0 Response by RECIST CRC N = 56 NE N = 31 Non CRC/Non-NE N = 43 All Patients N = 130 n (%) CR 0 ( 0.0) PR 5 ( 8.9)4 ( 12.9)3 ( 7.0)12 ( 9.2) SD 30 ( 53.6)24 ( 77.4)24 ( 55.8)78 ( 60.0) PD 21 ( 37.5)3 ( 9.7)16 ( 37.2)40 ( 30.8) CR + PR + SD 35 (62.5)28 (90.3)27 (62.8)90 (69.2)

Survival Estimates CRC – Median PFS 2.8 months [95% CI: ] – Median OS 9.4 months [95% CI: ] Neuroendocrine – Median PFS 14.6 months [95% CI: ] – Median OS 24.0 months [95% CI: ]

Kaplan-Meier Progression-Free Survival MONTHS K-M Estimate of Hepatic or Extra-Hepatic PFS Probability

Kaplan-Meier Overall Survival K-M Estimate of Survival Probability MONTHS

Conclusions TheraSphere demonstrated excellent tolerability and safety profile in patients with advanced metastatic liver disease Highly reliable delivery of planned radiation dose Prospective, multicenter confirmation of anti-tumor effect in patients without alternative therapeutic options Results were reproducible among all centers; set the stage for international, multicenter phase 3 RCTs