The Center for Personalized Diagnostics: Past, Present, and FUTURE

ALL in for ALL Patients: A Campaign for the CPD Campaign Goals: Sequence every ACC patient’s DNA Find more mutations Build out biobanks Make information accessible to all physicians Talking Points: How can the CPD help better treat ALL of our patients? The CPD is expanding patient populations that can benefit from CPD testing, while simultaneously advancing technology to enhance testing capabilities.

Center for Personalized Diagnostics: Lung Cancer 11% of patients analyzed by the CPD have been Lung Cancer Patients. The CPD tests tumor tissue for mutations relevant for immediate treatment and those that indicate possible resistance. What’s in Store for the Future: LUNG CANCER TARGETS EGFR ALK ROS1  ERBB2  BRAF PIK3CA And more to be discovered Next Generation Tests More Actionable Mutations Found Improved Targeted Therapies Better Clinical Outcomes

Center for Personalized Diagnostics: GI Cancer 10.5% of patients analyzed by the CPD have been GI Cancer Patients. The CPD is currently testing tumors for mutations that help find targeted therapies GI CANCER TARGETS KRAS EGFR BRCA CKIT BRAF And more to be discovered   What’s in Store for the Future: Next Generation Tests More Actionable Mutations Found Improved Combined Targeted Therapies More Clinical Trial Options Talking points for Gift officers: What specific therapies, and combined therapies, are being used when targetable mutations are discovered? These genes are on the solid V2 CPD panel.

Center for Personalized Diagnostics: Brain Cancer 7.0% of patients analyzed by the CPD are Brain/CNS Cancer Patients. The CPD tests for mutations with targetable treatments, as well as mutations that help establish the patient’s diagnosis. BRAIN CANCER TARGETS EGFR BRAF ATRX IDH1/2 And more to be discovered What’s in Store for the Future: Next Generation Tests More Actionable Mutations Found Improved Targeted Therapies More Clinical Trial Options Talking points for Gift officers: What specific therapies are being used when targetable mutations are discovered? (e.g CAR-T therapy against EGFR vIII mutation; ongoing trial at PENN) (e.g. FGFR inhibitors; Dovitinib) etc) Additional genes now on the solid V2 CPD panel.

Center for Personalized Diagnostics: Myeloid Leukemia 2.8% of patients analyzed by the CPD Are Acute Myeloid Cancer Patients The CPD tests for mutations that have prognostic, therapeutic, relapse, and monitoring implications. MYELOID TARGETS TP53 FLT3 PTEN NPM1 DNMT3a CKIT JAK2 And more to be discovered What’s in Store for the Future: Next Generation Tests More Actionable Mutations Found Improved Targeted Therapies More Clinical Trial Options Talking points for Gift officers: What specific therapies are being used when targetable mutations are discovered?

Center for Personalized Diagnostics: CLL, MM, and Lymphoma Current broad CPD panel to evaluate for CLL, MM, and Lymphoma Cancer Patients. The CPD needs to create specific, discrete panels for CLL, MM and Lymphoma. What is the status on CLL and MM tests/targets? What are the prognostic, therapeutic, relapse, and/or monitoring implications of mutation discovery? LYMPHOMA TARGETS TP53 PIK3CA PTEN BTK PLCG2 MYD88 BRAF JAK1/3 STAT3/5 And more to be discovered What’s in Store for the Future: Talking point: What specific therapies are being used when targetable mutations are discovered? In CLL, BTK mutations result in resistance to BTK inhibitors such as Ibrutinib. Such patients may benefit from BCL2 inhibitors e.g. Venetoclax or SYK inhibitors (e.g. Entosplenitib) Next Generation Tests More Actionable Mutations Found Improved Targeted Therapies More Clinical Trial Options

Center for Personalized Diagnostics: Breast Cancer 12.7% of patients analyzed by the CPD have been Breast Cancer patients. What is the status on breast cancer tests/targets? What are the prognostic, therapeutic, relapse, and/or monitoring implications of mutation discovery? BREAST CANCER TARGETS erbB, BRCA1/2, MET AKT1/2/3 CDKN2A MDM2 PDGFRA And more to be discovered What’s in Store for the Future: Next Generation Tests More Actionable Mutations Found Improved Targeted Therapies More Clinical Trial Options Talking points for Gift officers: What specific therapies are being used when targetable mutations are discovered? erbB (inhibitors can be used for erbB-mutated breast cancers. These genes are on the solid V2 CPD panel.

Center for Personalized Diagnostics: Ovarian Cancer Only 1% of patients analyzed by the CPD have been ovarian Cancer Patients. What is the status on ovarian cancer tests/targets? What are the prognostic, therapeutic, relapse, and/or monitoring implications of mutation discovery? OVARIAN CANCER TARGETS BRCA1/2, RET AKT1/2/3 CDKN2A MDM2 PDGFRA And more to be discovered What’s in Store for the Future: Next Generation Tests More Actionable Mutations Found Improved Targeted Therapies More Clinical Trial Options Talking points for Gift officers: What specific therapies are being used when targetable mutations are discovered? These genes are on the solid V2 CPD panel.

Center for Personalized Diagnostics: BRCA 40% of patients on which BRCA1/2 testing was done by the CPD showed disease-associated mutations - 25% of breast cancers tested - 55% of GI cancers tested How is the CPD utilizing BRCA mutation across different cancer types? What are the prognostic, therapeutic, relapse, and/or monitoring implications of mutation discovery? BRCA CANCERS Breast Ovarian Pancreatic GI Talking points for Gift officers: What specific therapies are being used when targetable mutations are discovered? BRCA mutations are relevant for patients who has Breast cancer, Ovarian cancer, Pancreatic cancer and other GI cancers. Next Generation Tests More Actionable Mutations Found Improved Targeted Therapies More Clinical Trial Options What’s in Store for the Future:

Center for Personalized Diagnostics: Melanoma 11.4% of patients analyzed by the CPD have been Melanoma Patients. What is the status on melanoma tests/targets? What are the prognostic, therapeutic, relapse, and/or monitoring implications of mutation discovery? MELANOMA TARGETS BRAF PTEN NRAS NF1 PIK3CA TERT And more to be discovered What’s in Store for the Future: Talking points for Gift officers: What specific therapies are being used when targetable mutations are discovered? BRAF mutations can be treated using (e.g. vemurafenib). These genes are on the solid V2 CPD panel. Next Generation Tests More Actionable Mutations Found Improved Targeted Therapies More Clinical Trial Options

Center for Personalized Diagnostics: Sarcoma Less than 1% of patients analyzed by the CPD have been Sarcoma Patients. What is the status on sarcoma tests/targets? What are the prognostic, therapeutic, relapse, and/or monitoring implications of mutation discovery? SARCOMA TARGETS MET PIK3CA PTPRD TP53 PDGFRA FOXO1-PAX3/7 And more to be discovered What’s in Store for the Future: Talking points for Gift officers: What specific therapies are being used when targetable mutations are discovered? Gene fusion identification can help assess prognosis: FOXO1-PAX3 gene fusion is associated with worse prognosis than FOXO1-PAX7 gene fusion Gene fusion identification can help establish a diagnosis of a specific subtype of sarcoma Next Generation Tests More Actionable Mutations Found Improved Targeted Therapies More Clinical Trial Options

Center for Personalized Diagnostics: GU Cancers 17.0% of patients analyzed by the CPD have been GU Cancer Patients. What is the status on GU tests/targets? What are the prognostic, therapeutic, relapse, and/or monitoring implications of mutation discovery? GU TARGETS TERT FGFR3 RAS PIK3CA And more to be discovered What’s in Store for the Future: Talking points for Gift officers: What specific therapies are being used when targetable mutations are discovered? These genes are on the solid V2 CPD panel. Detection of mutations in GU cancer can be applied to urine samples as an alternative to cytoscopy Specific mutations are associated with prognosis TERT and FGFR3 mutations are associated with recurrence of disease Next Generation Tests More Actionable Mutations Found Improved Targeted Therapies More Clinical Trial Options

Center for Personalized Diagnostics: Head and Neck Cancers 6% of patients analyzed by the CPD have been Head and Neck Cancer Patients. What is the status on Head and Neck cancer Tests/targets? What are the prognostic, therapeutic, relapse, and/or monitoring implications of mutation discovery? HEAD AND NECK TARGETS EGFR BRAF KRAS PIK3CA And more to be discovered What’s in Store for the Future: Talking points for Gift officers: What specific therapies are being used when targetable mutations are discovered? These genes are on the solid V2 CPD panel. Next Generation Tests More Actionable Mutations Found Improved Targeted Therapies More Clinical Trial Options

Center for Personalized Diagnostics: Neuroendocrine tumors (NETs) 1.5% of patients analyzed by the CPD have been NETs Patients. What is the status on NETs tests/targets? What are the prognostic, therapeutic, relapse, and/or monitoring implications of mutation discovery? NET Cancer TARGETS ATRX MEN1 ASCL1 TP53 MTOR PIK3CA And more to be discovered What’s in Store for the Future: Talking points for Gift officers: What specific therapies are being used when targetable mutations are discovered? Aggressive neuroendocrine tumors with BRAF mutations may be responsive to BRAF-MEK inhibitor combination therapy (e.g. Dabrafenib+trametib) These genes are on the solid V2 CPD panel. Next Generation Tests More Actionable Mutations Found Improved Targeted Therapies More Clinical Trial Options

Center for Personalized Diagnostics: Thyroid Cancer 7.3% of patients analyzed by the CPD have been Thyroid Cancer Patients. What is the status on thyroid tests/targets? How is the CPD partnering with the Center for Rare Cancers and Personalized Therapy? What are the prognostic, therapeutic, relapse, and/or monitoring implications of mutation discovery? THYROID TARGETS BRAF RET ALK PIK3CA, NTRK1/3 TP53 And more to be discovered What’s in Store for the Future: Talking points for Gift officers: What specific therapies are being used when targetable mutations are discovered? These genes are on the solid V2 CPD panel. Next Generation Tests More Actionable Mutations Found Improved Targeted Therapies More Clinical Trial Options

Center for Personalized Diagnostics: Cutaneous T cell Lymphoma (CTCL) 0 % of patients analyzed by the CPD have Been CTCL Patients. What is the status on CTCL tests/targets? What are the prognostic, therapeutic, relapse, and/or monitoring implications of mutation discovery? CTCL TARGETS JAK1/3 STAT3/5 TYK2 TP53 BRAF PLCG2 PTEN And more to be discovered What’s in Store for the Future: Talking points for Gift officers: What specific therapies are being used when targetable mutations are discovered? JAK1-mutated CTCLs may be treated using Jak inhibitors (e.g. Ruxolitinib) Next Generation Tests More Actionable Mutations Found Improved Targeted Therapies More Clinical Trial Options

The Future of the CPD Advance current technology to better locate mutations and understand how mutations work together Coordination of tissue procurement Enhance bioinformatic support Automation of work flow New sequencing equipment Integration of laboratory information system with EPIC Build technology to detect Circulating Tumor Cells Develop testing platforms to detect circulating tumor DNA for all solid tumors Resources to recruit, educate, train, and retain bioinformatics experts Recruit additional scientists in bioinformatics and computational diagnostics Establish training programs in computational personalized diagnostics