Canadian Chemical News: New Prescription

Chemistry | Pharmaceuticals
New
Prescription
NEOMED Institute of Montreal is attracting both public and private
investors to re-energize and streamline the drug discovery process.
30 November/December 2015 www.cheminst.ca/magazine
By Tim Lougheed
Chemisty | Pharmaceuticals
Paul Eifert
S
trategically wedged between
the many lanes of the TransCanada Highway and Pierre
Elliott Trudeau International
Airport at the west end of the island of
Montreal, the Saint-Laurent Campus of
Technoparc Montréal is this city’s bid to
establish a world-beating concentration
of research-intensive industries. The land
was set aside for this purpose in the late
1980s and addresses have steadily filled up
with high tech enterprises big and small.
The first international resident arrived
in 1996, as the Swedish pharmaceutical
firm Astra spent $330 million to build
and develop an ambitious facility that
would house nearly every aspect of the
drug discovery process, from fundamental
chemistry and biology to advanced testing
on animals.
Within a few years Astra had merged
with the British multinational Zeneca
as giants of the global pharmaceutical
industry began to grapple with the growing
difficulties of finding new products to bring
to market. Such mergers led to a surplus of
research capacity and a subsequent trend
to reduce the size of operations around the
world. A number of the affected sites were
in Montreal, including AstraZeneca’s in
Technoparc Montréal, which shut its doors
at the end of 2012.
The story could easily have ended
there, with a fully outfitted 12,500 squaremetre building sitting empty on a piece
of prime real estate. Today, however, the
parking lot is full. About 200 people work
in this building on various aspects of drug
discovery or development — about a third
more than AstraZeneca ever employed
there. Several are former AstraZeneca
staff members who took up the challenge
of finding new ways of turning pharmaceutical prospects into marketable products.
That challenge has proved to be vexing
for the major players in this field, who are
A protein purification system used by researchers at Montreal’s NEOMED Institute.
sometimes portrayed as fat cats turning out
drugs on billion-dollar budgets. The reality
is somewhat harsher: these corporate giants
have traditionally spent a great deal of time
and money exploring the pharmaceutical
potential of various compounds only to
end, as the process usually does, in failure. A
high failure rate is ultimately essential to the
success of any kind of drug discovery — the
better to avoid bringing an unsafe or ineffective drug to market — but the associated
financial risks have become profound, which
is why this corporate sector has worked so
hard to reorganize and in some cases reinvent the way it does business.
AstraZeneca’s abandonment of its
Montreal digs reflected just this kind of
corporate realignment. And although that
is no longer where the company directly
engages in the grass roots search for new
drugs, the building is home to more of this
activity than ever before.
The driving force that has maintained
this research momentum is the NEOMED
Institute, a not-for-profit body that has
brought public and private investors into
the most fundamental biological and
chemical aspects of the drug discovery
process. The organization now oversees some $90 million worth of funding
and in-kind contributions that include
partnerships with universities, hospitals and major pharmaceutical firms,
including AstraZeneca, Pfizer, Janssen and
GlaxoSmithKline.
NEOMED’s business model is premised
on bridging the often profound divide that
separates the commercialization of new
drugs from the basic scientific research
that reveals the raw materials that make
up those drugs. Although the organization’s website and printed literature are
illustrated with images of famous bridges
from around the world, the analogy is more
www.cheminst.ca/magazine November/December 2015 31
Chemistry | Pharmaceuticals
samples for more detailed analysis at Montreal’s NEOMED Institute.
than colourful rhetoric. The need to span
this gap has become a priority critical to the
survival of the pharmaceutical industry,
which now enthusiastically supports
external researchers who can share the
risks of studying complex chemicals that
may be able to work wonders within the
even more complex human body.
As if that mandate weren’t daunting
enough, NEOMED has also committed
itself to building up the business and technology ecosystem that nurtures the top
researchers it needs. In addition to housing
the industrial expertise of its own staff,
the building has also invited other businesses to set up shop under the same roof.
These independent companies include
small start-ups specializing in areas such
as medicinal chemistry, biological testing
and pharmacokinetics, as well as a law firm
specializing in biotechnology and intellectual property. They likewise benefit from
access to a corporate facility outfitted with
everything from impressive boardrooms to
an outstanding cafeteria.
The Quebec government was one of
the prime movers behind the creation
of NEOMED at the end of 2012, just
as AstraZeneca was preparing to leave
Technoparc Montréal. The company’s
parting gift was the building and most of
its installed equipment, which enabled the
new organization to hit the ground running
with a ready-made headquarters.
Even more importantly, AstraZeneca
transferred ownership of some of its
advanced research projects, thereby
providing NEOMED with a similarly
ready-made scientific agenda. Several of
these projects are approaching the point
of clinical testing, which might never
have happened if no one had been there to
continue the work.
Philippe Walker, NEOMED’s chief
scientific officer, has a favourite example
of the progress that has taken place:
a compound that goes by the name
NEO6860. It is what pharmaceutical
researchers call an antagonist, which
means that it stymies the normal operation
32 November/December 2015 www.cheminst.ca/magazine
Paul Eifert
A compound purification system that employs liquid chromatography to prepare
of biochemical channels in the body to
gain some medical advantage. In this case,
NEO6860, which acts at the TRPV1 ion
channel, interferes with one of the mechanisms that generate the painful symptoms
of diseases such as osteoarthritis.
This ion channel is well known, but
previous efforts to shut it down have met
with unacceptably severe side effects,
including an increase in body temperature
and dangerous impairment of an individual’s ability to feel heat. Over the last decade,
Walker says, AstraZeneca’s Montreal operation had been working on an entirely new
approach based on selective blocking of the
ion channel. “We found a compound that
blocks only the capsaicin activation but
doesn’t block pH or heat activation, unlike
other compounds that were tested before,”
he says, noting that these features should
prevent side effects. (Capsaicin is the active
ingredient in hot chili peppers.)
Walker’s own background illustrates
the rich brain trust that now populates the
robust infrastructure that NEOMED inherited. “The site is like a giant toolbox for us
to advance programs,” he says.
Walker, who worked for AstraZeneca
in Montreal from the early 1990s until
2012, once led the company’s worldwide
neuroscience drug discovery efforts, overseeing about 650 researchers in Canada,
Sweden and the United States. Among
those researchers was Andrew Griffin, an
AstraZeneca chemist who counts himself
as being among the last handful of people
still working in the building at the end
of 2012. Griffin was part of the team that
discovered NEO6860 and is excited to
be seeing it through to what should be a
commercial future.
Griffin appreciates Walker’s comparison of NEOMED to a multidisciplinary
toolbox that can move the results of pure
science toward the realm of applied clinical investigation. Nevertheless, he is fond
of admitting some bias toward the value
of his own discipline in overcoming the
Paul Eifert
Chemisty | Pharmaceuticals
Nuclear Magnetic Resonance scanning confirms the molecular structure of agents studied at Montreal’s NEOMED Institute.
fundamental difficulties associated with any
drug discovery project. “This process fails for
a number of different reasons,” Griffin says.
“The biology of the human body may not
accommodate what a new drug is supposed
to do; new approaches may prove to show
no additional benefit compared to successful
agents on the market doing the same thing;
or there may be some problem with pharmacokinetics, or unwanted side effects. In many
cases these issues come down to the molecule itself, meaning it’s the responsibility of
the chemist who designs these molecules in
the first place.”
In this light, it should come as no
surprise that the search for drugs comes
with a high price tag. Griffin’s former boss
at AstraZeneca, Bill Brown, still works just
down the hall from him and echoes this
assessment. “The easy stuff’s been done,”
says Brown. “It’s getting harder to find drugs,
to do science. The targets are more difficult,
the chemistry is more difficult. It becomes
more expensive and it’s a risky business to
start with. And at the end of the day big
pharma has stockholders to answer to.”
NEOMED has its own bills to pay, but
its mission departs from the traditional
business model. As opposed to a single
corporate entity taking on all the risk to
bring a new product to market, an investment shared by public and private sector
partners reduces the cost of such risk. The
building itself is home to a wide variety of
firms, so the necessary help might be no
more than a staircase away.
In this way NEOMED has provided
hope to researchers looking for ways across
that unwelcome expanse that separates
their promising ideas and inventions from
the rigid economics and regulations of the
pharmaceutical marketplace. For example,
although the organization’s AstraZeneca
site originally specialized in work on pain
relief, the launch of NEOMED soon
attracted the attention of people working
at a vaccine development site operated by
GlaxoSmithKline in the nearby Montreal
suburb of Laval, which was also slated for
closure. The emerging collaboration has
enabled that site to stay in business and
NEOMED to expand its horizons. “Before
that, NEOMED was only able to attack
small-molecule drug discovery programs,”
says Walker. “But with the expertise we get
through that new interaction, we can now
develop vaccines or potentially antibodies
through our biology program.”
At the same time, Walker points out
that NEOMED is not immune to the ruthless economics of drug development, which
still consumes a lot of cash. Attracting
private firms to put up some of that cash
means cultivating a research environment
that is more attractive than anything they
could maintain for themselves. “You must
have an indigenous innovation capability
because that’s what’s going to drive business
development,” says Walker. “Big companies will come to you because you’re doing
things better, faster and in a more intelligent
manner than other places.”
www.cheminst.ca/magazine November/December 2015 33