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care companies, sees the efforts as part of a
growing trend to repurpose. “That all leads
to the possibility of a lot shorter investment
cycle, and potentially a very different pricing
point, and lots of possibilities for rare diseases
where there just hasn’t been enough of a fi-
nancial incentive,” she says. “And that has lots
of appeal.” Eric Kandel of the Kavli Institute
for Brain Science at Columbia University, a
winner of the Nobel Prize in physiology or
medicine who is an adviser to Pharnext, says
that the startup is at the leading edge of the
trend, calling its methodology “both original
and powerful.” As for whether that approach
will catch on widely, Kandel adds, “We should
know soon.”
A
T THE DAWN of modern genetic re-
search, almost no one anticipated
the enormous complexity in the
biology of disease. Many research-
ers thought the genome would be a kind of in-
struction manual for the body. Pioneers such
as Celera Genomics’ Craig Venter and Francis
Collins of the National Institutes of Health
were celebrated as “gene hunters,” a term that
evoked crusaders scouring the globe for that
one “silver bullet” gene that would explain—
and facilitate a cure for—a given disease.
To some extent, these researchers found
real treasure. Geneticist Nancy Wexler, for
example, spent years in Venezuela compiling
family trees of those affected by Huntington’s
disease, a rare, inherited condition. Her work
led to the discovery of the mutation in a single
gene that predicts whether an individual will
contract the condition.
But scientists soon realized that genetic
maps were less like an instruction manual and
more like the parts catalog you get with Ikea
furniture. What’s more, researchers discovered
other catalogs that added complex variables to
the relationships between genes and disease—
for example, the proteome, the proteins en-
coded by DNA, and the transcriptome, all the
nucleic acids that convert DNA into proteins.
The morning-after disappointment has
proved wrenching, as researchers learned
that complex diseases, such as cancer and
Alzheimer’s, didn’t yield to a single gene. (Even
Huntington’s, its gene identified, has remained
untreatable.) Today, Cohen and others see a
link between the obsession with simplicity
and a decline in drug discovery. That decline
shows itself in the 1-in-10 success rate for FDA
those results, in February the U.S. Food and Drug Administration
granted Pharnext “fast track” status for that therapy—an acceler-
ated review process, awarded only when the agency thinks a drug
demonstrates “superior effectiveness” in treating a serious disease
It is, to be sure, only one hopeful step against one rare ail-
ment. Still, technology has shortened Pharnext’s path in ways
with promising long-term implications, shaving years off the
drug-design timeline. Preclinical testing and clinical trials
generally take eight to 10 years, and developing a novel drug
completely from scratch can add seven years to the process,
sometimes much more. In the case of PXT3003, in contrast,
A.I. helped Pharnext select three existing drugs to repurpose:
baclofen, a muscle relaxant; naltrexone, used to treat opioid
dependence; and sorbitol, a glucose reduction used as a laxa-
tive. Because the drugs were already in use, Pharnext could skip
the Phase I trials normally required to ensure their safety—and
eliminate the “build from scratch” stage.
FDA fast-tracking increases the odds that PXT3003 could be
on the market as soon as 2020—and it’s only one of Pharnext’s
many projects. The company will soon begin a second Phase II
trial of a drug with indications for Alzheimer’s and a first
Phase II trial for an ALS therapy, in both cases using a similar
repurposed combination.
Just as important: If these experiments succeed, copycats with
deeper pockets could follow suit. Kathleen Sebelius, a secretary
of Health and Human Services in the Obama administration
who is now a consultant and board member for several health
To help find therapies, A.I.-driven startups build maps that show how
genes, proteins, and the body interact as diseases progress. This illus-
tration depicts Pharnext’s map for CMT, a neurodegenerative condition.
pathways
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