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PHARMA, BIOTECH & LIFE SCIENCE
09.15
SEPTEMBER 2015 : VOLUME 11 : NUMBER 9
PUBLISHED SINCE 2005
CONTRACT SERVICES
36
Double-dealing in immunotherapy
AstraZeneca strikes pair of
deals to strengthen its
immunotherapy portfolio
BY ZACK ANCHORS
LONDON--
AstraZeneca announced two
deals in August oriented toward bolstering
its offerings in the immunotherapy space.
The company struck a $500-million deal with
Heptares Therapeutics Aug. 6 that will give
it exclusive global rights to an experimen-
tal cancer drug. Days earlier, the company
announced that MedImmune, its global bio-
logics research and development arm, had
entered into a clinical trial collaboration with
Mirati Therapeutics to investigate the safety
and efficacy of using two experimental drugs
in combination to treat lung cancer.
The licensing agreement with Heptares,
a clinical-stage drug discovery and devel-
opment company, allows AstraZeneca to
develop, manufacture and commercialize
HTL-1071, a compound targeting the mol-
ecule adenosine in order to stimulate the
A2A receptor found on the surface of T cells.
"The A2A receptor program at Heptares
has been an outstanding example of our
structure-based drug design approach in
action, resulting in a novel clinical candidate,
HTL-1071, with a highly attractive profile,"
said Malcolm Weir, CEO of Heptares. "Hep-
tares is targeting G-protein-coupled recep-
tors that play a key role in cancer biology
through the identification of both antibody
and small-molecule therapeutics."
HTL-1071's potential as an effective cancer
treatment is found in its ability to halt one of
the processes that prevents T cells from pro-
liferating and destroying cancer cells. Typi-
cally, tumor cells use the molecule adenosine
to stimulate the A2A receptors found on T
cells, disrupting their anti-cancer response.
By blocking A2A receptors, HTL-1071 may be
able to limit the role of adenosine in driving
tumor growth.
AstraZeneca says it will explore the
potential effectiveness of HTL-1071 to treat
a wide range of cancers. It will also evaluate
its efficacy when used in combination with
In Florida, an antibiotic/
antitumor connection; in
California, a bacterial
enzyme that might fight
nicotine addiction
BY MEL J. YEATES
JUPITER, Fla.--
Scientists from The Scripps
Research Institute (TSRI) Florida campus
have shown an "unprecedented mechanism"
for how a natural antibiotic with antitumor
properties incorporates sulfur into its molec-
ular structure. This new discovery could
open the way to incorporating sulfur into
other natural products, potentially advancing
new therapies for indications beyond cancer.
The study, which was led by TSRI profes-
sor Ben Shen, was recently released online
ahead of print by the journal Proceedings of
the National Academy of Sciences. "We found
a novel mechanism to incorporate sulfur into
natural products," according to Shen. "Until
our study, we didn't really know how sulfur
atoms are incorporated into a natural prod-
uct--now we have discovered a new family of
enzymes and have a workable mechanism to
account for sulfur incorporation into a larger
class of polyketides that include many drugs
such as erythromycin (antibacterial) and lov-
astatin (cholesterol-lowering)."
The study is focused on leinamycin
(LNM), a sulfur-containing antitumor
antibiotic produced by a species of the soil-
dwelling bacterium Streptomyces. The Shen
laboratory has been studying the potential
of this natural compound for development
of anticancer drugs.
"In an earlier study, we have also showed
that an engineered analogue of LNM (LNM
E1) could act as a prodrug activated by cel-
lular reactive oxygen species to cause DNA
damage and cancer cell death," says Shen.
"The LNM scaffold and its unprecedented
sulfur-mediated mode of action will serve as
the basis for further drug discovery efforts."
"The sulfur-incorporation mechanism
discovered in our study revealed the novel
function of a polyketide synthase, greatly
expanding our understanding of its chemis-
try," said Ming Ma, one of the co-first authors
of the study and a member of the Shen lab.
"Since polyketide synthases are a large family
of enzymes that have been proven amenable
for polyketide structural diversity and drug
discovery, it is particularly exciting that this
new discovery now provides the possibilities
of adding sulfur atoms to compounds simi-
lar to leinamycin or other polyketide natural
products."
Polyketide synthases (PKSs) link directly
to a complex series of chemical reactions that
ultimately add sulfur to leinamycin. Shen
tells DDNews that the discovery is based on
long-term research into key steps in LNM
biosynthesis. Their discovery of the C-S bond
cleaving polyketide synthase domain in LNM
expands the current toolbox for developing
novel polyketide natural products.
Leinamycin is a unique natural product,
not only for its chemical structure but also
for its antitumor mechanism. The unique
features of LNM are mainly concentrated in
its sulfur-containing dithiolane moiety, which
kills by interfering with the cancer cell's DNA.
PKSs are the key enzymes responsible for the
construction of the polyketide backbones of
the polyketide family of natural products from
DOUBLE CONTINUED ON PAGE 16
Getting ahead with GPCRs ..................................................8
Geneuity adopts Thermo's next-gen tech
and Oncomine assay ..........................................................38
Oh say can you see, Watson? ..........................................40
On the cutting edge.............................................................42
22
WHAT'S INSIDE
DISCOVERY 6
TOOLS & TECHNOLOGY
PRECLINICAL 17
RESEARCH & DEVELOPMENT
12
CLINICAL TRIALS
28
DIAGNOSTICS 33
BUSINESS & GOVERNMENT POLICY
40
FINANCE/MARKETS 3
EDITORIAL/COMMENTARY 10
PRODUCTS & SERVICES
45
Bicoastal discoveries from Scripps
AstraZeneca inked two deals recently in the cancer immunotherapy space. Pictured here is the
Gaithersburg, Md.-based headquarters of MedImmune--the global biologics research and
development arm of AstraZeneca--which forged one of those two deals.
Scripps Research Institute professor Kim Janda (center), graduate student Song Xue (left) and
research associate Joel Schlosburg (right) were authors of a new paper exploring a bacterial
enzyme that might be used as a drug candidate to help people quit smoking.
TSRI CONTINUED ON PAGE 09
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