Innovation for the Individual: The Rise of Companion Diagnostics

Inherited genetic variation is a fundamental of biology and both drives and reflects the process of evolution. Layered upon inherited variation is somatic
or acquired variation. Variability in DNA – whether inherited or acquired – underpins functional differences in biological processes and is particularly
significant in the treatment of human disease.

One of the core tenets of medicine is to “do no harm.” Yet, it’s well understood that a drug without side effects does not exist and probably never will.
In other words, most drugs, however efficacious, are accompanied by some degree of toxicity, ranging from mild to severe. Thus, logic and practicality has
driven the development of biological signposts or “biomarkers” to indicate which patients a drug should and should not be administered to.

Inherent in the concept of a companion diagnostic is the partnership between a drug and a biomarker-based diagnostic test. The first real example of
co-development was that of the drug trastuzumab, targeted to the oncogene HER2 and the HER2 genetic tumor test. The companion diagnostic allows targeting
of the drug to only those patients who overexpress HER2 and have an aggressive form of breast cancer, and led to simultaneous FDA approval of both drug
and diagnostic. The success of this companion diagnostic approach galvanized the field of personalized medicine.

Today, the co-development of drugs and companion diagnostics has captured the imagination of the healthcare industry, regulators and payers to a point
where these institutions are aligning around improving outcomes for patients. More than 50 percent of oncology drugs in development are proceeding with
some form of companion diagnostic. At Myriad, for example, we have more than 20 ongoing collaborations with pharmaceutical companies to help them develop
companion diagnostic tests for their medicines. And, we’re expanding our companion diagnostic research beyond cancer into other therapeutic areas including
autoimmune disorders, diabetes and neuroscience.

The evolution of this complex ecosystem has been rapid and reflects a shift in industry focus from the old school “trial and error” drug development
process to understanding the molecular basis of a given disease, the isolation of a biological target and development of specific therapies for that
target. Myriad Genetics is excited to be using its broad expertise in RNA analysis, DNA sequencing and proteomics to lead in the discovery of new
biomarkers and the revolution in companion diagnostics.

Only a few years back, there was an apocryphal witticism that “pharmaceutical companies see companion diagnostics as the future of drug development – and
they intend to keep it that way.” Fortunately, this sentiment has not been echoed in my many productive companion diagnostic collaborations with dedicated
pharmaceutical scientists over the last 10 years. Whether the general reduction in R&D productivity has driven the love affair with companion
diagnostics or whether there has been a specific need to rescue a failed drug through deeper understanding of its mechanism of action is irrelevant now.

The paradigm has shifted.

Jerry Lanchbury, Ph.D.

Chief Scientific Officer

Myriad Genetics, Inc.