CAMBRIDGE, Mass.,
Sept. 26, 2016 /PRNewswire/ -- Infinity Pharmaceuticals,
Inc. (NASDAQ: INFI) today announced initial clinical and new
preclinical data for IPI-549, an orally administered
immuno-oncology development candidate that selectively inhibits
PI3K-gamma. Preliminary Phase 1 results from nine patients with
advanced solid tumors show that the safety, pharmacokinetics and
pharmacodynamics of IPI-549 monotherapy treatment appear favorable.
Additionally, new preclinical data demonstrate that IPI-549 can
reverse tumor resistance to checkpoint inhibitors, providing
additional rationale for the planned evaluation of IPI-549 in
combination with a checkpoint inhibitor in the ongoing Phase 1
study. These data are being presented in a poster session at the
Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy
Conference: Translating Science into Survival taking place in
New York City.
"While there have been recent advancements in therapies as a
result of our understanding of the immune response to cancer,
additional treatments are needed that can improve survival for more
patients," stated Anthony Tolcher,
M.D., FRCP(C), clinical director at South Texas Accelerated
Research Therapeutics and an investigator for the IPI-549 Phase 1
clinical study. "The initial Phase 1 monotherapy data for IPI-549
are encouraging, and I look forward to the upcoming initiation of
the first cohort evaluating IPI-549 in combination with a
checkpoint inhibitor."
"As the only PI3K-gamma inhibitor in clinical development,
IPI-549 offers a unique approach to enhancing the anti-tumor immune
response. Our preclinical findings suggest that IPI-549 remodels
the immune-suppressive tumor microenvironment, primarily through
its effects on myeloid cells, leading to enhanced anti-tumor T cell
activity and cytokine production, all of which play critical roles
in immune response," stated Jedd
Wolchok, M.D., Ph.D., Chief of the Melanoma and
Immunotherapeutics Service at Memorial Sloan Kettering Cancer
Center (MSK), as well as Associate Director of the Ludwig Center
for Cancer Immunotherapy and Director of the Parker Institute for
Cancer Immunotherapy, both at MSK. Dr. Wolchok is also a scientific
collaborator on the IPI-549 program and lead investigator for the
Phase 1 clinical study. "Data also demonstrate that the effects of
IPI-549 on the tumor microenvironment reverse resistance to
checkpoint inhibition in multiple preclinical models, providing
further rationale for evaluating this combination therapy in
patients."
The ongoing Phase 1 clinical study of IPI-549 is designed to
explore safety, tolerability, pharmacokinetics and pharmacodynamics
of IPI-549 as a monotherapy and in combination with an anti-PD-1
antibody, a checkpoint inhibitor, in approximately 175 patients
with advanced solid tumors, including non-small cell lung cancer
(NSCLC), melanoma and squamous cell carcinoma of the head and neck
(SCCHN).1 The monotherapy dose-escalation portion of the
study is continuing, and Infinity expects to initiate cohorts
studying IPI-549 in combination with an anti-PD-1 antibody this
fall.
Although there has been great progress in the treatment of
cancer, there remains a need for additional treatment options.
NSCLC, melanoma and SCCHN account for more than 17 percent of all
new cancer cases in the U.S.2,3
Summary of Early Phase 1 Clinical Data Presented for
IPI-549
The poster, "IPI-549-01: A Phase 1/1b first-in-human
study of IPI-549, a PI3K-gamma inhibitor, as monotherapy and in
combination with an anti-PD1 antibody in subjects with advanced
solid tumors,"4 included data from nine patients with
advanced solid tumors who received monotherapy treatment with
IPI-549, with doses ranging from 10 mg once daily (QD) to 20 mg
QD.
No dose limiting toxicities and no serious adverse events have
occurred. Six of nine patients remain on study, with a maximum
exposure of 24 weeks at the time of analysis. Pharmacokinetic and
pharmacodynamic data support once daily dosing of IPI-549 based on
the observed half-life and inhibition of the PI3K-gamma
pathway.
Summary of New Preclinical Data Presented for
IPI-549
The poster, "The PI3K-gamma inhibitor, IPI-549,
increases antitumor immunity by targeting tumor-associated myeloid
cells and remodeling the immune-suppressive tumor
microenvironment,"5 includes new data further
elucidating the mechanism of action for IPI-549 and demonstrating
the synergy between IPI-549 and checkpoint inhibitors in multiple
preclinical models.
Preclinical studies show that resistance to checkpoint
inhibition is associated with increased numbers of myeloid cells,
and that IPI-549 treatment is able to reverse the lack of response
in tumor models that are insensitive to checkpoint inhibitors.
These findings provide further rationale for studying IPI-549 in
combination with an anti-PD-1 antibody (a type of checkpoint
inhibitor) in the clinic.
Preclinical data also demonstrate that treatment with IPI-549
leads to a shift in tumor-associated myeloid cells from the
immunosuppressive phenotype (M2 phenotype) to the proinflammatory
phenotype (M1). Additionally, treatment with IPI-549 also increases
the frequency of tumor-specific T cells and increases the
production of proinflammatory cytokines. These findings lend
support to the hypothesis that inhibition of PI3K-gamma by IPI-549
leads to an activated and more efficient anti-tumor immune response
through its effects on the immune-suppressive tumor
microenvironment.
About IPI-549
IPI-549 is an orally administered
immuno-oncology development candidate that selectively inhibits
PI3K-gamma. In preclinical studies, IPI-549 inhibits
immune-suppressive macrophages within the tumor microenvironment,
whereas other immunotherapies such as checkpoint modulators more
directly target immune effector cell function. As such, IPI-549 may
have the potential to treat a broad range of solid tumors and
represents a potentially complementary approach to restoring
anti-tumor immunity in combination with other immunotherapies such
as checkpoint inhibitors.
IPI-549 is an investigational compound and its safety and
efficacy has not been evaluated by the U.S. Food and Drug
Administration or any other health authority.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within the
meaning of The Private Securities Litigation Reform Act of 1995
including those regarding the company's expectations about the
timing and type of data presentations, the therapeutic potential of
PI3K-gamma inhibition and of IPI-549, alone or in combination with
other agents, initiation of cohorts studying IPI-549 in combination
with an anti-PD-1 antibody this fall, and the safety,
pharmacokinetics and pharmacodynamics of IPI-549 monotherapy
treatment. 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, including, for example, that there is no guarantee
that IPI-549 will successfully complete necessary preclinical and
clinical development phases, or gain regulatory approval and other
risks 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 August 9, 2016, 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.
Contact:
Jaren Irene
Madden, Senior Director,
Investor Relations and Corporate Communications
617-453-1336 or Jaren.Madden@infi.com
1 www.clinicaltrials.gov, NCT02637531
2 American Cancer Society, Cancer Facts and
Statistics 2016,
http://www.cancer.org/research/cancerfactsstatistics/cancerfactsfigures2016/index
and
http://www.cancer.org/cancer/skincancer-melanoma/detailedguide/melanoma-skin-cancer-key-statistics,
Last Accessed September 14, 2016.
3 Conquer Cancer Foundation, Head and Neck Cancer
Statistics,
http://www.cancer.net/cancer-types/head-and-neck-cancer/statistics,
Last Accessed September 14, 2016.
4 Tochler, A., Hong D., Sullivan R, et al.
IPI-549-01: A Phase 1/1b first-in-human study of IPI-549, a
PI3K-gamma inhibitor, as monotherapy and in combination with an
anti-PD1 antibody in subjects with advanced solid tumors. Presented
at Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy
Conference: Translating Science into Survival (Poster B070),
2016.
5 Rausch, M., Tchaicha, Tibbitts, T. et al. The
PI3K-gamma inhibitor, IPI-549, increases antitumor immunity by
targeting tumor-associated myeloid cells and remodeling the
immune-suppressive tumor microenvironment. Presented at Second
CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference:
Translating Science into Survival (Poster B032), 2016.
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