We rely on natural human genetic variation as a
proxy for—and method of more accurately predicting—the physiologic effects of
therapies in humans.
We identify variants in drug target genes that
recapitulate drug effects and then execute PheWAS to find all phenotypes
(diseases) across the human phenome (based on PheWAS codes derived from
ICD-9/10 codes and manually grouped to define clinical phenotypes) that are
associated with carrying at least one copy of a minor allele.
Our team with relevant qualifications and
content-specific knowledge perform evidence reviews and curate the results for
key associations. We execute comprehensive searches of a wide range of
databases and other resources, including thorough review of de-identified
patient medical records of associated cases.
Once we establish a preliminary precision
indication/subphenotype and a hypothesis about the disease mechanism,
appropriate Vanderbilt experts are identified and approached to serve as
investigators that will move projects into animal or human validation studies
with precise endpoints to confirm the mechanism.
Most of the projects we are pursuing intend to
leverage the 505(b)(2) regulatory approval pathway, which allows the sponsor to
rely, in part, on existing data from approved drugs. This can eliminate
the need for preclinical studies, shorten the overall FDA approval time, and
Once of the goals of our federal funding (CTSA
award No. UL1TR000445 from the National Center for Advancing Translational
Sciences) is to assess the program’s pace of achieving downstream regulatory
and commercialization milestones compared to traditional methods).
Some of our portfolio projects have initiated Phase II clinical trials in less than two years since project inception.