Molecular Diagnostics

Transcription

1 Technology verview January, 2011

2 Molecular Diagnostics ovel Approach to Discovery of Antibody Biomarkers Innovative platform technology, licensed from UTSW Broadly applicable for the discovery of disease-specific autoantibodies and synthetic molecules that capture them from the blood Initially targeting diseases for which there is no definitive blood test, or where existing diagnostic approaches are invasive and inaccurate Simple blood tests for Alzheimer s Disease, multiple forms of cancer, and other conditions are in advanced development on-exclusive collaboration with BMS for lead Alzheimer s test Potential to develop highly targeted therapeutics and vaccines which can be delivered directly to the targeted autoimmune cells ngoing trials to support development and commercialization 2

3 Proprietary Antibody Capture Technology Capture Agent + Can we identify synthetic compounds that act as antigen surrogates? 3

4 Antibody Background The immune response amplifies antibodies that recognize disease-specific molecules (antigens) B Cell Receptor B Cells Foreign Antigen Amplification Antibodies (100s of millions) 4

5 Technology verview Proprietary Antibody Capture Technology Discovery of Autoantibody-Ligand Pairs Identifies synthetic compounds that act as antigen surrogates Microarray Spot Capture Agent Healthy Control Samples + Fluorescent Anti-IgG + Diseased Patient Samples Synthetic molecule microarray + Fluorescent Anti-IgG Synthetic molecule microarray 5

6 Alzheimer s Disease Proof of Concept Demonstrated ability to differentiate Alzheimer s patients Three molecules identified that distinguish Alzheimer s patients from age-matched controls ADP1 and ADP3 bind antibodies distinct from those bound by ADP2, i.e., two AD-specific autoantibodies have been discovered Lupus Parkinson s Healthy, on-demented Alzheimer s 6

7 Alzheimer s Disease Further Validation ngoing validation study with positive initial results (140 samples) Intensity Conducting 580 patient sample validation study 200 AD, 200 matched controls, 180 other diseases Final results expected by late 2011 Potential to launch test in 2013 ADP2 Intensity Intensity ADP1 ADP3 7

8 Potential for Early Diagnosis in MCI Patients Intensity (X10 3 ) LewyBody Dementia AD C LBD Patients 8

9 Development of A Commercially Viable ELISA Assay HRP Colorless substrate Blue Product AD A. B. ormal Intensity Intensity Serum Dilution Serum Dilution

10 Broadly applicable diagnostic platform Discovery of Cancer Specific Antibodies 70 Four peptoids found to distinguish SCLC patients in an initial study Intensity (X10 3 ) LCP1 LCP2 LCP3 LCP4 0 Lung Cancer Healthy Lupus Alzheimer s Four peptoids found to distinguish Stage I pancreatic cancer patients in an initial study Intensity (X10 3 ) Pancreatic Cancer Healthy Alzheimer s 10

11 Synthesis of Peptoid Libraries H R R n Peptides Peptoids n PEG-coated polystyrene (TentaGel) H2 H 3 C H CH 3 H 2 S H H H 2 H H Figliozzi, et al. (1996) Methods Enzymol. 267, , livos, et al. (2002) rg. Lett. 4,

12 Demanding High Selectivity: Identification of VEGR2-Binding Peptoids H R 6 262,144 (8 6 ) Compounds H 2 4 H 2 4 H H 2 Methoxyethylamine (mea) Piperonylamine (pip) Fufurylamine (f fa) 1,4-Diaminobutane (lys) (R)-Methylbenzylamine (mba) H Tryptamine (trp) VEGFR-2 Expressing Cells VEGFR-2 on- Expressing Cells Allyamine (all) Isobutylamine (leu) 12

13 Advisory Board Richard Lerner, M.D. President of The Scripps Research Institute Tom Kodadek, Ph.D. Professor of Chemistry, The Scripps Research Institute Pascal Goldschmidt, M.D. Dean, University of Miami School of Medicine Tahir Ahmed, M.D. Professor of Pulmonary Medicine, University of Miami School of Medicine Roger Kornberg, Ph.D. Professor of Medicine, Stanford Medical School Chi-Huey Wong, Ph.D. President, Academia Sinica, Taiwan 13