CAMBRIDGE, Mass., Jan. 20, 2017 /PRNewswire/ -- Today, during
a plenary session at the Keystone Symposia Conference, "PI3K
Pathways in Immunology, Growth Disorders and Cancer," Infinity
Pharmaceuticals, Inc. (NASDAQ: INFI) presented preclinical data for
IPI-549, an oral immuno-oncology development candidate that
selectively inhibits phosphoinositide-3-kinase-gamma (PI3K-gamma).
Preclinical data showed that IPI-549 is able to help overcome
resistance to checkpoint inhibition by remodeling the
immune-suppressive tumor microenvironment primarily through its
effects on myeloid cells, a type of cell considered to be involved
in suppressing immune response against tumors. Initial Phase 1
monotherapy data from nine patients with advanced solid tumors were
also summarized and showed that the safety, pharmacokinetics and
pharmacodynamics of IPI-549 monotherapy treatment appeared
favorable. IPI-549 is believed to be the only PI3K-gamma inhibitor
in clinical development.
These preclinical data provide a compelling rationale for
Infinity's ongoing Phase 1 clinical study designed to evaluate
IPI-549 as a monotherapy and in combination with Opdivo®
(nivolumab), a PD-1 immune checkpoint inhibitor, in patients with
advanced solid tumors. The combination portion of the Phase 1 study
will include patients with non-small cell lung cancer (NSCLC),
melanoma, and squamous cell carcinoma of the head and neck (SCCHN)
whose tumors show initial resistance or subsequently develop
resistance to immune checkpoint therapy. There is a great need for
additional treatment options for the growing number of patients
living with these cancers, which account for more than 17 percent
of all new cancer cases in the U.S.1,2
"While new immunotherapies, such as T cell checkpoint
inhibitors, are showing great promise in the treatment of various
cancers, there are multiple mechanisms of immune tolerance in
tumors. Additional treatment options are needed for patients who
relapse or do not respond to currently available therapies," stated
Jeffery Kutok, M.D., Ph.D., vice
president of biology and translational science at Infinity
Pharmaceuticals and a plenary speaker at the conference. "The data
presented suggest that targeting PI3K-gamma by IPI-549 within
immune-suppressive myeloid cells in the tumor microenvironment
could offer a unique way to both enhance the activity of checkpoint
inhibition in sensitive tumors, as well as to overcome tumor
resistance to checkpoint inhibition. Infinity is excited to be at
the forefront of developing a potentially transformative approach
within immuno-oncology, and we look forward to reporting additional
data from our Phase 1 study of IPI-549 later this year."
The tumor microenvironment, or TME, refers to the non-cancerous
cells present in the tumor. Cells within the TME, including
immune-suppressive myeloid cells, can provide growth signals to
tumor cells, as well as signals that inhibit an anti-tumor immune
response. The presence of the supportive TME is believed to be one
reason why some cancer therapies do not provide durable or
effective results. Targeting the immune-suppressive myeloid cells
represents an emerging approach within the field of cancer
immunotherapy, and inhibition of PI3K-gamma represents a novel
approach to targeting the immune-suppressive microenvironment.
Summary of Today's Presentation
In a presentation
entitled "The PI3K-gamma inhibitor, IPI-549, increases antitumor
immunity by targeting tumor-associated myeloid cells and overcomes
immune checkpoint blockade resistance in preclinical models," Dr.
Kutok reviewed data previously published in two Nature
articles3,4 and presented at the Second
CRI-CIMT-EATI-AACR International Cancer Immunotherapy
Conference.5,6
Preclinical data showed that macrophage PI3K-gamma signaling
promotes immune suppression by inhibiting activation of anti-tumor
T cells. Blocking PI3K-gamma activated the immune response and
significantly suppressed growth of tumors in preclinical models.
These data demonstrate that PI3K-gamma plays a key role in cancer
growth and also help to further elucidate the mechanism of action
for IPI-549.
Preclinical data also demonstrated that resistance to immune
checkpoint blockade is directly mediated by the suppressive
activity of tumor-infiltrating myeloid cells in a number of
preclinical tumor models and confirmed that immune-suppressive
myeloid cells play a critical role in resistance to checkpoint
inhibitors. Furthermore, the data showed that inhibition of
PI3K-gamma by IPI-549 switched the activation of myeloid cells from
an immune-suppressive state to a pro-inflammatory state, leading to
enhanced anti-tumor cytotoxic T cell activity, particularly when
combined with checkpoint inhibitors. Thus, in preclinical models,
IPI-549 treatment is able to overcome resistance to checkpoint
inhibition. These findings provide further rationale for the
ongoing Phase 1 study of IPI-549 in combination with checkpoint
inhibitors.
Phase 1 clinical data from nine patients treated with IPI-549
administered as a monotherapy at doses ranging from 10 mg once
daily (QD) to 20 mg QD were also summarized during the
presentation. As of the September
2016 data cutoff, no dose limiting toxicities and no serious
adverse events were observed. Pharmacokinetic and pharmacodynamic
data supported once daily dosing of IPI-549 based on the observed
half-life and inhibition of the PI3K-gamma pathway.
About the IPI-549 Phase 1 Study
The ongoing Phase 1
clinical study of IPI-549 is designed to explore the activity,
safety, tolerability, pharmacokinetics and pharmacodynamics of
IPI-549 as a monotherapy and in combination with Opdivo®
in patients with advanced solid tumors. The study includes
monotherapy and combination dose-escalation phases, in addition to
expansion cohorts, and is expected to enroll approximately 175
patients.
The IPI-549 monotherapy dose-escalation phase is expected to be
completed in the first half of 2017, and the monotherapy expansion
phase in patients with advanced solid tumors is anticipated to
begin in the second half of the year. Once the dose-escalation
phase evaluating IPI-549 plus Opdivo is completed, an expansion
phase is planned to evaluate the combination in patients with
select solid tumors, including non-small cell lung cancer (NSCLC),
melanoma and squamous cell carcinoma of the head and neck (SCCHN).
Patients enrolled in expansion cohorts evaluating IPI-549 plus
Opdivo represent a difficult-to-treat population, as they must have
demonstrated initial resistance or subsequently develop resistance
to a PD-1 or PD-L1 therapy immediately prior to enrolling in the
study.
About IPI-549
IPI-549 is an investigational, orally
administered immuno-oncology development candidate that selectively
inhibits PI3K-gamma. In preclinical studies, IPI-549 increases
antitumor immunity by targeting tumor-associated myeloid cells and
overcomes immune checkpoint blockade resistance in preclinical
tumor models. 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. A Phase 1 study of IPI-549 in patients with advanced
solid tumors is ongoing.7
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.
About Infinity
Infinity is an innovative
biopharmaceutical company dedicated to advancing novel medicines
for people with cancer. Infinity is developing IPI-549, an oral
immuno-oncology development candidate that selectively inhibits
PI3K-gamma. A Phase 1 study in patients with advanced solid tumors
is ongoing. For more information on Infinity, please refer to
Infinity's website at www.infi.com.
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, clinical trial plans regarding IPI-549. 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 November 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.
OPDIVO® is a registered trademark of Bristol-Myers
Squibb.
Contact:
Jaren Irene
Madden, Senior Director, Investor Relations and Corporate
Communications
617-453-1336 or Jaren.Madden@infi.com
1 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 29, 2016.
2 Conquer Cancer Foundation, Head and Neck Cancer
Statistics,
http://www.cancer.net/cancer-types/head-and-neck-cancer/statistics,
Last Accessed September 29, 2016.
3 Kaneda, M., Messer, K., Ralainirina, N., Li, H., et
al. PI3Kγ is a molecular switch that controls immune suppression.
Nature, 2016 Nov;539:437–442.
4 De Henau, O., Rausch, M., Winkler, D., Campesato, L.,
et al. Overcoming resistance to checkpoint blockade therapy by
targeting PI3Kγ in myeloid cells. Nature, 2016
Nov;539:443-447.
5 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.
6 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.
7 www.clinicaltrials.gov, NCT02637531.
To view the original version on PR Newswire,
visit:http://www.prnewswire.com/news-releases/infinity-presents-preclinical-data-and-phase-1-clinical-data-on-ipi-549-at-pi3k-keystone-symposia-conference-300394215.html
SOURCE Infinity Pharmaceuticals, Inc.