Infinity Pharmaceuticals, Inc. (NASDAQ: INFI) today announced new
preclinical data showing the activity of IPI-145, its oral inhibitor of
phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma, in models of
diffuse large B-cell lymphoma (DLBCL) and T-cell acute lymphoblastic
leukemia (T-ALL), two difficult-to-treat hematologic malignancies (blood
cancers) for which limited treatment options are available.
Additionally, Phase 1 clinical data of IPI-145 in 14 patients with
advanced aggressive non-Hodgkin lymphoma (aNHL) were reported, with
early clinical activity observed in patients with DLBCL, Richter
transformation and transformed follicular lymphoma. These findings were
presented today at the 55th Annual Meeting of the American Society of
Hematology (ASH).
“The preclinical data reported today, as well as early clinical data in
aggressive non-Hodgkin lymphoma, further underscore the potential of
IPI-145 to treat a broad range of blood cancers,” stated Julian Adams,
Ph.D., president of R&D at Infinity. “IPI-145 has already shown clinical
activity in indolent non-Hodgkin lymphoma and chronic lymphocytic
leukemia, and we are advancing IPI-145 in late-stage development in
these two indications. The preclinical data reported today are expanding
our understanding of the mechanism of action of IPI-145 and the roles of
PI3K-delta and PI3K-gamma, which will help inform further clinical
development.”
Early Clinical Data in aNHL and Preclinical Data in DLBCL
Early Phase 1 data in aNHL and preclinical data in DLBCL were reported
in the presentation “The potent PI3K-delta,gamma inhibitor, IPI-145,
exhibits differential activity in diffuse large B-cell lymphoma (DLBCL)
cell lines” (Abstract #1832). Phase 1 data in 14 patients with aNHL
showed that IPI-145 led to a reduction in adenopathy (decrease in the
size of lymph nodes) in three of eight patients with DLBCL and two of
three patients with Richter transformation. A partial response in one of
three patients with transformed follicular lymphoma was also reported.
IPI-145 was generally well tolerated, and the majority of side effects
were low grade, asymptomatic and transient. The most common ≥ Grade 3
side effects in these patients were neutropenia (32 percent), febrile
neutropenia, diarrhea, fatigue, pneumonia, increased ALT/AST (two liver
enzymes) and dyspnea (9 percent each).
Preclinical studies showed that treatment with IPI-145 suppressed PI3K
signaling and cell growth in a subset of DLBCL cell lines. In several of
these cells lines, treatment with IPI-145 and ibrutinib (a Bruton's
tyrosine kinase, or BTK, inhibitor) led to a synergistic suppression of
cell growth, providing a potential rationale for exploring IPI-145 in
combination with ibrutinib in DLBCL.
Preclinical Data in T-ALL
In the presentation “The potent PI3K-delta,gamma inhibitor, IPI-145,
exhibits preclinical activity in murine and human T-cell acute
lymphoblastic leukemia” (Abstract #1438), data from preclinical studies
of IPI-145 tested in both human and rodent cell lines of T-ALL showed
that treatment with IPI-145 inhibited the growth of a subset of T-ALL
cells deficient for PTEN (a phosphatase and tumor suppressor gene).
Treatment with IPI-145 led to a greater inhibition of T-ALL cell growth
compared to treatment with molecules selective for only PI3K-delta or
PI3K-gamma, providing a potential rationale for combined PI3K-delta and
-gamma inhibition for the treatment of T-ALL.
In a separate press release issued today, Infinity reported updated
Phase 1 data in patients with indolent non-Hodgkin lymphoma (iNHL) which
showed that IPI-145 was clinically active, with an overall response rate
of 73 percent (11 of 15 evaluable patients) and a 20 percent complete
response rate (3 of 15 patients). Eight patients (53 percent) remain
progression-free for over one year. Additionally, translational data
showed that IPI-145 affects key signaling molecules in the tumor
microenvironment, providing a potential mechanistic rationale for the
clinical activity of IPI-145 observed in patients with iNHL and chronic
lymphocytic leukemia (CLL).
The posters presented at the 55th Annual Meeting of ASH are available in
the Publications Archive on Infinity’s website http://www.infi.com/product-candidates-publications.asp.
About the Development of IPI-145 for the Treatment of Blood Cancers
Infinity is developing IPI-145, an oral inhibitor of Class I
PI3K-delta,gamma. The PI3Ks are a family of enzymes involved in multiple
cellular functions, including cell proliferation and survival, cell
differentiation, cell migration and immunity. The PI3K-delta,gamma
isoforms are preferentially expressed in leukocytes (white blood cells),
where they have distinct and mostly non-overlapping roles in immune cell
development and function. Targeting PI3K-delta and PI3K-gamma may
provide multiple opportunities to develop differentiated therapies for
the treatment of hematologic malignancies as well as inflammatory
diseases.
Infinity has launched DUETTS, a worldwide investigation of IPI-145 in
blood cancers. As part of the DUETTS program, Infinity is currently
enrolling patients in DYNAMO, a Phase 2 monotherapy study designed to
evaluate the safety and efficacy of IPI-145 in patients with refractory
indolent non-Hodgkin lymphoma (iNHL) (ClinicalTrials.gov Identifier
NCT01882803), and DUO, a Phase 3 monotherapy study designed to evaluate
the safety and efficacy of IPI-145 in patients with relapsed/refractory
chronic lymphocytic leukemia (CLL) (ClinicalTrials.gov Identifier
NCT02004522).
An investigator-sponsored Phase 1b, open-label study of IPI-145 in
patients with B-cell NHL, CLL and T-cell lymphoma in combination with
rituximab (a monoclonal antibody therapy), bendamustine (a chemotherapy)
or both rituximab and bendamustine is also open for enrollment
(NCT01871675).
Additionally, a Phase 1 study of IPI-145 in patients with advanced blood
cancers is ongoing (NCT01476657).
About Infinity Pharmaceuticals, Inc.
Infinity is an innovative biopharmaceutical company dedicated to
discovering, developing and delivering best-in-class medicines to people
with difficult-to-treat diseases. Infinity combines proven scientific
expertise with a passion for developing novel small molecule drugs that
target emerging disease pathways. For more information on Infinity,
please refer to the company’s website at www.infi.com.
Forward-Looking Statements
This press release contains forward-looking statements within the
meaning of The Private Securities Litigation Reform Act of 1995. Such
forward-looking statements include those regarding the Company’s
expectations about: its ability to execute on its strategic plans; the
therapeutic potential of PI3K inhibition and IPI-145; and the potential
rationale of investigating IPI-145 in additional indications and
combinations therapies. Such statements are subject to numerous
important factors, risks and uncertainties that may cause actual events
or results to differ materially from the company’s current expectations.
For example, there can be no guarantee that Infinity will report data in
the time frames it has estimated, that any product candidate Infinity is
developing will successfully complete necessary preclinical and clinical
development phases, or that development of any of Infinity’s product
candidates will continue. Further, there can be no guarantee that any
positive developments in Infinity’s product portfolio will result in
stock price appreciation. Management’s expectations and, therefore, any
forward-looking statements in this press release could also be affected
by risks and uncertainties relating to a number of other factors,
including the following: Infinity’s results of clinical trials and
preclinical studies, including subsequent analysis of existing data and
new data received from ongoing and future studies; the content and
timing of decisions made by the U.S. FDA and other regulatory
authorities, investigational review boards at clinical trial sites and
publication review bodies; Infinity’s ability to obtain and maintain
requisite regulatory approvals and to enroll patients in its clinical
trials; unplanned cash requirements and expenditures; development of
agents by Infinity’s competitors for diseases in which Infinity is
currently developing or intends to develop its product candidates; and
Infinity’s ability to obtain, maintain and enforce patent and other
intellectual property protection for any product candidates it is
developing. These and other risks which may impact management’s
expectations are described in greater detail under the caption “Risk
Factors” included in Infinity’s quarterly report on Form 10-Q filed with
the Securities and Exchange Commission (SEC) on November 7, 2013, and
other filings filed by Infinity with the SEC. Any forward-looking
statements contained in this press release speak only as of the date
hereof, and Infinity expressly disclaims any obligation to update any
forward-looking statements, whether as a result of new information,
future events or otherwise.
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