Notes

Slide Show

Outline

1	Recombinant Fusion Constructs for Cancer Therapy Development of a Commercial Pipeline in an Academic Setting Michael G. Rosenblum, Ph.D Immunopharmacology and Targeted Therapy Laboratory Department of Experimental Therapeutics M.D. Anderson Cancer Center Houston, Texas
2
3	ITT Developmental Pipeline:
4	What’s in the Pipeline?
5	Over 20 different Targeted Therapeutics under development. Partial Listing: HuM195/rGel Leukemia(AML, CML) Phase I-MDACC VEGF/rGel All Solid Tumors IND /Phase 1 scfvMEL/TNF Melanoma, Breast IND/Phase 1 ML3-9/rGel Breast, Pancreatic Pre-Clinical rGel/BLyS B-Cell Tumors Pre-clinical ML3-9/TNF Breast Pancreatic Pre-clinical scfvMEL/rGel Melanoma, Breast Pre-clinical VEGF/TNF All Solid Tumors Pre-clinical GrB/scFvMEL Melanoma, Breast Pre-clinical GrB/VEGF All Solid Tumors Pre-clinical IIP45/rGel All Tumors Pre-clinical
6	Over 20 different Targeted Therapeutics under development. Partial Listing(2): Anti-HERV/rGel HERV antigens/Breast Pre-Clinical Anti-FGFR3/rGel Multiple Myeloma/Bladder Pre-Clinical GrB/BLyS B-Cell Tumors Pre-clinical scfvMEL/rGel Melanoma, Breast Pre-clinical GrB/scFvMEL Melanoma, Breast Pre-clinical GrB/IIP45 Glioblastoma/Breast Pre-clinical Aptamer/rGel PSMA/Prostate/vasculature Pre-Clinical Anti-CEA/rGel Colon, Breast Pre-Clinical ZME-Fullerenes Melanoma, Breast Pre-Clinical bHCG/rGel Ovarian Pre-Clinical bHCG/TNF Ovarian Pre-Clinical GrB/bHCG Ovarian Pre-Clinical
7
8	Angiogenesis Overview Formation of new blood vessels Required for many normal physiological processes Setting up vasculature of the embryo Wound healing Disorders: - Diabetic retinopathy - Rheumatoid arthritis - Tumor Growth
9	A “Trojan Horse” was developed composed of the VEGF growth factor and the rGel Toxin
10	Co-Localization of VEGF/rGel (green) and Blood Vessels (red) in MDA-MB-231Tumors
11
12
13
14
15
16	Imaging-Guided Phase II Evaluation of VEGF₁₂₁/rGel- A “Personalized Medicine” Approach
17
18	scFvMEL/TNF Immunocytokine
19
20
21	Protocol 2006-0343 IRB Approved on 8/06 PI- Luis Camacho, M.D. A Phase I Dose Finding Study to Evaluate the Pharmacokinetics, Toxicity, and Anti-Tumor Activity of scFvMEL/TNF for the Treatment of GP240 Positive Malignancies Primary Endpoints: 1) To evaluate the toxicities and tolerability of scFvMEL/TNF in patients with gp240-overexpressing metastatic melanoma and lobular breast carcinoma. 2) To assess the pharmacokinetics 3) To establish the MTD and DLT of scFvMEL/TNF Secondary Endpoints: 1)To determine the degree of apoptosis or tumor necrosis before and after treatment with scFvMEL/TNF. 2)To evaluate the anti-tumor activity of scFvMEL/TNF 3)To evaluate the occurrence and frequency of human anti-mouse (HAMA) and anti-TNF (HATA) antibodies.
22	Advantages of an Academic Pipeline: We take the risks Translational products can be outlicensed at multiple stages Excellent opportunities for Academic: Commercial Interaction More Control over go/no go decisions Faster Track to clinical products(?)