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Phase I Clinical Trial of IPI-504

Posted by Julie Royster (jroyster) on Apr 23 2006
GIST In the News >>
  -- Novel Treatment Paradigm Has Potential to Address Resistance to Current
Targeted Therapies --

CAMBRIDGE, Mass., Jan. 10 /PRNewswire/ -- Infinity Pharmaceuticals, Inc.
today announced the initiation of a second Phase I clinical trial of IPI-504,
the company's Heat Shock Protein 90 (Hsp90) inhibitor and lead investigational
anti-cancer agent. This study, part of the Company's evolving oncology
development program, will evaluate the safety, pharmacokinetic profile and
potential efficacy of IPI-504 in patients with gastrointestinal stromal tumors
(GIST) resistant to Gleevec(R) (imatinib mesylate).
This open-label, dose-escalation Phase I clinical trial of IPI-504 is
being conducted at Dana-Farber Cancer Institute in Boston, Mass. under the
direction of George Demetri MD, Director of the Center for Sarcoma and Bone
Oncology at Dana-Farber. "We are very excited about this Phase I clinical
trial of IPI-504 in patients with refractory GIST as it pioneers a novel
treatment paradigm for these patients with an unmet medical need," said Dr.
Demetri. "Previous treatments for GIST have been dramatically effective but
over time we have seen the emergence of resistance to targeted therapy such as
Gleevec(R), and this leads to progression of the cancer. IPI-504 has an
important new mechanism of action with the potential to treat patients with
resistant disease. Even more importantly, GIST may serve as a bellwether of
activity, since the mechanism of action of IPI-504 may also apply to patients
with breast cancer resistant to Herceptin(R), lung cancer resistant to
Tarceva(R), and multiple myeloma resistant to VELCADE(R)."
In preclinical work performed in collaboration with Dr. Jonathan
Fletcher's lab at Brigham and Women's Hospital in Boston, Mass., Infinity
Pharmaceuticals has demonstrated that IPI-504 kills GIST cancer cells as
effectively as Gleevec(R) in vitro. Moreover, when cancer cells have
mutations rendering them resistant to Gleevec(R), IPI-504 kills these cells
with even greater effectiveness. The more mutated the GIST cells become, the
more sensitive they are to IPI-504. These data were presented at the NCI-
AACR-EORTC Molecular Targeting Meeting in November 2005.
"The initiation of this additional Phase I trial of IPI-504 represents an
important milestone for our lead product candidate and a significant
validation of our strategy to discover and develop therapies that attack
cancer cell survival mechanisms," said Julian Adams, Ph.D., Chief Scientific
Officer, Infinity. "We are delighted to be collaborating with Dr. Demetri and
his outstanding team of scientists and caregivers at the Dana-Farber on this

About IPI-504
IPI-504 is Infinity's novel anti-cancer agent that potently and
selectively inhibits Hsp90. IPI-504 has broad anti-tumor activity in animal
models as a single agent as well as in combination with existing anti-cancer
therapeutics. Research shows that inhibition of Hsp90 forces cancer cells to
"commit suicide" through a process of programmed cell death or apoptosis. In
addition to Gleevec(R)-resistant GIST, IPI-504 is currently undergoing
evaluation as a monotherapy for relapsed or relapsed, refractory multiple
myeloma in a multi-center Phase I dose-escalation trial. Interim data from
the first Phase I trial of IPI-504 was presented in December 2005 at the
American Society of Hematology (ASH) Annual Meeting.

About Gastrointestinal stromal tumors (GIST)
The American Cancer Society (ACS) reports that GIST is the most frequent
form of gastrointestinal sarcoma, a life-threatening disease highly resistant
to traditional chemotherapy or radiation treatment. In the majority of cases,
specific mutations in cellular signaling enzymes called KIT or PDGFRA allow
the survival signal of the mutated cancer cell to be switched "on" all the
time. Both KIT and PDGFRA are signaling enzymes which belong to the class of
"tyrosine kinases" and are responsible for sending growth and survival signals
inside the cell. The mutations in KIT or PDGFRA allow the GIST cells to grow
uncontrollably and spread (metastasize). The initial identification of
tyrosine kinase mutations in GIST has allowed for the development of targeted
kinase inhibitors, such as Gleevec(R), as an effective treatment of the
disease. However, over time new kinase mutations evolve so that the targeted
kinase inhibiting drugs are no longer effective at treating the disease. The
ACS estimates that between 4,500 and 6,000 Americans develop GIST each year.

About Infinity Pharmaceuticals, Inc.
Infinity Pharmaceuticals is an innovative cancer drug discovery company
that leverages its strength in small molecule drug technologies to bring
important new medicines to patients.

Editor's Note: This release is available in the Media Room of the Infinity
website at

Adelene Q. Perkins Paul Kidwell (media)
Chief Business Officer Kidwell Public Relations
Infinity Pharmaceuticals, Inc. 617-296-3854

SOURCE Infinity Pharmaceuticals, Inc.
Web Site:

Last changed: Apr 23 2006 at 3:06 PM


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