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Tranzyme MATCHes up with Bristol-Myers
Squibb
January 2010
EDIT CONNECT
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RESEARCH TRIANGLE PARK, N.C.—Virtually all drug discovery
and development concentrates on one of two classes of
compounds—small molecules
that are easy to administer but frequently not very good at binding to targets,
or large molecules like proteins and peptides
that provide highly specific
therapeutic action and very high binding potential but are expensive, unstable
with short half-lifes in vivo and seldom
suitable for oral administration. Tranzyme Pharma thinks macrocyclic molecules
can provide a third way—a "tweener" if you will—and Bristol-Myers Squibb
has
bought into the idea by entering into a strategic collaboration agreement with
the company to discover, develop and commercialize novel macrocyclic
compounds.
The collaboration will
deploy Tranzyme's proprietary drug
discovery technology, Macrocyclic Template Chemistry (MATCH), to identify and
develop new drug candidates for
multiple targets in diverse therapeutic areas.
Under the terms of the agreement, Tranzyme will be primarily
responsible for early lead discovery, and Bristol-Myers Squibb will take
primary
responsibility for optimizing the identified lead compounds. BMS will
be solely responsible for completing preclinical and clinical development of
all
products arising from the collaboration, and for their commercialization
globally. The company will provide an upfront payment of $10 million and an
additional $3 to $6 million in research funding to Tranzyme for an initial
two-year term. Tranzyme will receive further funding if the agreement is
extended beyond the initial term. In addition, Tranzyme is eligible to receive
development and regulatory milestones and tiered royalties for each
product
resulting from the collaboration. Total milestone payments under the agreement,
excluding royalties, could reach up to approximately $80
million for each
target program.
The goal
of the collaboration is to explore the molecular
chemistry space accessed by MATCH to discover novel bioactive macrocycles.
These macrocycles represent
a distinct and underexplored compound class that
displays favorable characteristics exhibited by large biomolecules, such as
high potency and
selectivity, while maintaining the benefits typically
associated with small-molecule drugs, such as high oral availability and low
cost of goods.
"Macrocyclic compounds are 'large small
molecules,'"
explains Dr. Vipin K. Garg, Tranzyme's president and CEO. "Being cyclic
stretches the molecule and locks it in shape. This complexity
and rigidity
prevents the molecule from flip-flopping in space and increases affinity with
the target."
Macrocyclic drugs have been around a long time, he
notes—cyclosporine, for example—
but most of them were discovered in nature by a
hit-or-miss discovery process, not synthesized in the lab. Using its
high-throughput MATCH assay,
Tranzyme has developed a library of between 25,000
and 30,000 macrocyclics that provide the initial roadmap to indicate whether or
not there has been a
good hit to a specific target, Garg says. After this
initial phase, the molecule can be optimized.
Tranzyme Pharma's own pipeline is derived from its MATCH
technology and targets two
validated GPCR drug targets, ghrelin and motilin,
explains Dr. Helmut Thomas, senior vice president of R&D. Two drugs are in
the clinic, with one
nearing Phase III and the other in Phase II clinical
trials.
"There are always concerns about safety, toxicity and oral
bioavailability," notes Thomas, but so far all have proven to be good.
Code: E011022 Back |
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