127Comprehensive phenotyping is important for understanding disease mechanisms
and variations in disease course and response to therapy among patients. SurroMed
Inc’s phenotyping technology platform provides fundamental information about
disease and enables rapid discovery of new and useful biological markers. These
biological markers will have utility for better diagnosing and treating disease and
developing new and improved therapeutic products.
Metaprobe™ biomarkers (Phenome Sciences) offer an improved approach to
identifying a patient’s phenotype. Metaprobes measure the capacity of targeted
pathways that are instrumental in a disease process or metabolic pathway relevant
to the activity of a pharmaceutical. Structurally, Metaprobe biomarkers are small
molecules such as amino acids or other compounds that have confi rmed safety pro-
fi les and can be delivered orally, by injection, or by inhaler. Metaprobes are labeled
to quantify pathway capacity by detection of release tags in breath, plasma, or
urine. The rate of appearance of the release tag gives a direct and quantitative mea-
surement of the in vivo activity of the targeted pathway, creating a dynamic bio-
marker of phenotype. Metaprobes are available for over 120 pathways in various
stages of active development. For example, metaprobes can provide very sensitive
assessment of physiologic response to a known therapeutic that changes internal
demand for glutathione. Metaprobe biomarkers have been demonstrated in the fol-
lowing paradigms:
- Identifi cation of a large population with strong effi cacy and no signifi cant side
effects, allowing smaller, faster trials with higher odds of success - Characterization of optimal dosage from Phase II trials in order to increase the
success rate in phase III trials - Mechanism confi rmation with safety information from fi rst-in-man tests, leading
to better phase II study design - Selection of the best drug candidates from animal studies for clinical develop-
ment, enhancing drug discovery productivity - Completion of mechanism-based discovery to understand novel pathways as
potential drug targets, enabling effective translation of genomics information
into drug creation
Effi cient and comprehensive large-scale phenotyping technologies are needed to
understand the biological function of genes. This presents a diffi cult challenge
because phenotypes are numerous and diverse, and they can be observed and anno-
tated at the molecular, cellular and organismal level. New technologies and
approaches will therefore be required. Efforts to develop new and effi cient tech-
nologies for assessing cellular phenotypes include the following: - A phenotypic map can be generated to correspond to any genotypic map. Some
genes have only one corresponding phenotype whereas most genes have many
corresponding phenotypes. - The most complete gene annotation is available for simple microbial-cell
systems. - Phenotype microarray technology enables the testing of thousands of
phenotypes.
Role of Pharmacogenetics in Pharmaceutical Industry