Xconomy.com
Protagonist Criss-Crosses Pacific,
in Search of New Peptide Drugs
Luke Timmerman, 7/11/12
I
f your definition of hard work
depends on getting to the office at 7 am every day, then
Dinesh Patel might sound pretty
lazy. He doesn’t usually pull out of
his driveway for work until 9 am.
He has a business reason for starting late, and it has little to do with
beating traffic (although that’s a
nice bonus). The reason is that his
company, Menlo Park, CA-based
Protagonist Therapeutics, has half
of its scientific team located 17
hours ahead in Brisbane, Australia.
And if you want people in different
countries and time zones to work
on the same page, it helps to get
them on a daily work rhythm that’s
at least somewhat similar.
“When it’s 3 pm in California, it’s 8
am the next day in Australia, so we
have a lot of good time working together from 3 pm to 7 pm our time,”
Patel says. “It’s challenging, but
once you master the distance, there
are advantages.” (One advantage is
getting work done around the clock.
The downside? Occasional afterdinner business calls.)
Protagonist, founded in 2007 by
researcher Mark Smythe in Bris-
bane, has found a way to make
progress in this unusual structure
for a biotech startup. The company
has raised about $9 million from a
set of investors in Australia (Starfish
Ventures, QBF, and IMB) as well
as a name more familiar in the
states, Lilly Ventures. The investment, and a couple of drug discovery partnerships with Cambridge,
MA-based Ironwood Pharmaceuticals (NASDAQ: IRWD) and Copenhagen, Denmark-based Zealand Pharma, has come together
around Protagonist’s idea for making new peptide drugs. These
drugs are being designed so that
they can be given as oral pills, or to
hit molecular targets that were very
tough to bind with, or might only
have been reachable in the past
with injectable protein drugs.
It’s a complex drug discovery challenge. But if Protagonist can keep
its small team of 22 people working
on it seamlessly in two countries, it
could end up with a big payoff. The
ultimate prize would be oral pills
against autoimmune disorders that
affect millions of people.
“We want to make oral peptide
drugs. It feels good to say that, but
it’s a challenging task. We believe
we are ready,” Patel says.
Patel has a long history of biotech
entrepreneurship, as a co-founder
of Vicuron Pharmaceuticals and
Miikana Therapeutics, companies
that ended up being acquired by
Pfizer for $1.9 billion, and by Entremed for $39 million, respectively.
Based on his experience in managing partnerships with drug companies, researchers, and contract research firms around the world, Patel
says he developed a personal bias
toward companies that have global
footprints. So when he was approached about becoming Protagonist’s CEO late in 2008, his first reaction to the Aussie connection
wasn’t “Geez, I’ll have to spend a lot
of time on planes.”
“Most people shy away from
these kind of arrangements, for
me it was an added attraction,”
Patel says. “It’s a personal bias, but
I think there’s much to be gained
from different cultures and different
setups. Most find it challenging with
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Dinesh Patel, CEO of
Protagonist Therapeutics
the
s time zones and travel. For me,
it’s fun going to Brisbane.”
Traveling to Brisbane might sound
pretty good to an American tourist,
but of course it takes real commitment to make a startup prosper
when it has small teams so far
apart. So Patel has made sure to
keep the Aussie and American
teams integrated on a daily basis.
“I don’t want us to do ‘A’ in one
place and ‘B’ in another. On purpose I’m doing cross pollination. It
really encourages scientists to
work together,” Patel says.
Protagonist’s teams are working
together on “disulfide rich peptides” which can be engineered
to have convenient drug properties, either as oral pills, or infrequent injections patients can give
themselves under the skin. Most
companies tend to focus on either small molecule drugs made
through chemical synthesis, or
genetically engineered “large
molecule” proteins, while shying
away from peptides that could be
classified as “mid-sized.” That’s
because chemists haven’t traditionally been able to make peptides into convenient oral pills
(like small molecules), and it has
been tough to keep them stable
in the bloodstream for long periods commonly seen with larger
protein drugs. But the idea of
making peptides that combine
the best of both small and large
molecules has been pursued by
a number of startups for some
time—Cambridge,
MA-based
Aileron Therapeutics is one
member of the class—and Ironwood and Zealand have both
had success overcoming some
challenges with peptides.
Protagonist has sought to bring
together a computational program
to design the peptide molecules,
coax them into millions of different
shapes and sizes in phage libraries, and then use medicinal chemistry techniques to tweak molecules
to get the ideal drug properties.
The company isn’t saying much
about the specifics of what it is
working on, but Patel gave some
sense of its direction when we
spoke a couple weeks ago at the
Biotechnology Industry Organization conference in Boston. Ironwood, for example, has its orallyavailable peptide drug, linaclotide,
that aims at a molecular target for
irritable bowel syndrome called
GC-C. But irritable bowel syndrome, and other diseases of the
gut, are usually the result of many
different kinds of proteins being
out of whack, in need of inhibition
or stimulation. Various inflammatory protein molecules called cytokines—IL-6, IL-23, and tumor necrosis factor—are three particularly good targets, Patel says. “We
envision huge applications,” for
autoimmune diseases, Patel says.
Protagonist’s partnerships, so far,
are pretty traditional discovery
deals in which it does some of the
early-stage R&D, and then hands
over molecules for its partner to
take further in development. Essentially, he wants his small team
to do a few things, and do them
well, rather than get overextended.
And the deals are structured so
that Protagonist has the freedom
to develop some of its own drugs,
meaning the employees get the
potential upside of working for a
biotech startup. Now that’s an idea
the Australian and American
teams can surely agree on, over a
pint in Australia or Silicon Valley. ■
Luke Timmerman is the National
Biotech Editor of Xconomy. You
can reach him at [email protected] or follow
him on Twitter @ldtimmerman.
Reprint courtesy of:
www.protagonist-inc.com
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