HAYWARD, Calif. and
CAMBRIDGE, Mass., June 26, 2018 /PRNewswire/ -- Arcus Biosciences,
Inc. (NYSE: RCUS), a clinical-stage biopharmaceutical company
focused on creating innovative cancer immunotherapies, and Infinity
Pharmaceuticals, Inc. (NASDAQ: INFI), a clinical-stage
biopharmaceutical company developing IPI-549, a first-in-class
immuno-oncology product candidate that selectively inhibits
phosphoinositide-3-kinase gamma (PI3K-gamma), today announced that
they have entered into a clinical collaboration to evaluate two
triple combination therapies in selected tumor types which
typically show minimal response to checkpoint inhibition
monotherapy.
The collaboration will evaluate IPI-549 in combination with
AB928, Arcus's dual adenosine receptor antagonist, and AB122,
Arcus's anti-PD-1 antibody, as well as IPI-549 in combination with
AB928 and chemotherapy in patients with triple negative breast
cancer (TNBC) or ovarian cancer in four separate cohorts. These
four cohorts will be incorporated into Arcus's recently initiated
Phase 1/1b trial to evaluate AB928
combinations in TNBC and ovarian cancer. As both macrophages and
high adenosine levels are believed to play critical roles in
creating a highly immune-suppressive tumor microenvironment in TNBC
and ovarian cancer, the triple combinations being evaluated could
represent a promising approach to treating these tumor types.
By intervening in multiple mechanisms that mediate
immuno-suppression, the companies hope to address two tumor types
that lack effective therapies, particularly in later lines of
treatment.
"This partnership with Infinity is important as, for the first
time, we will be investigating the potential for the triple
combination of a selective PI3K-gamma inhibitor, a dual adenosine
receptor antagonist, and either a PD-1 inhibitor or chemotherapy to
effectively treat patients with triple negative breast cancer or
ovarian cancer," said Terry Rosen,
Ph.D., Chief Executive Officer of Arcus Biosciences. "This
collaboration also allows us to expand the number of promising
combinations with strong biological rationale that we plan to
evaluate in our recently initiated Phase 1/1b trial for AB928. Arcus has carefully
considered which immuno-oncology therapies can best target immune
suppressive macrophages and has concluded that selective inhibition
of PI3K-gamma is a fundamental mechanism for reprogramming
macrophages from a pro-tumor to an anti-tumor function."
"This collaboration with Arcus Biosciences enables an important
expansion of our clinical development of IPI-549, investigating
IPI-549 in triple-combination therapy with other important
immuno-oncology agents as well as with chemotherapy," said
Adelene Perkins, Chief Executive
Officer and Chair of Infinity Pharmaceuticals.
"Combining these agents may result in enhanced reduction of
pro-tumor immune suppression and increased anti-tumor immune
activation. We look forward to working with the terrific team
at Arcus in investigating these triple-combination therapies as
potentially new treatment options for patients with cancers that
are not adequately addressed by existing therapies."
Under the terms of the agreement, Infinity and Arcus will share
equally expenses related to the four triple-combination cohorts to
evaluate the safety and activity of IPI-549 + AB928 + AB122 and
IPI-549 + AB928 + chemotherapy. Each of the four triple-combination
cohorts will enroll approximately 15 patients. Topline data from
these studies are expected in 2019.
About AB928
AB928 is an orally
bioavailable, highly potent antagonist of the adenosine 2a and
2b receptors. The activation of these
receptors by adenosine interferes with the activity of key
populations of immune cells and inhibits an optimal anti-tumor
immune response. By blocking these receptors, AB928 has the
potential to reverse adenosine-induced immune suppression within
the tumor microenvironment. AB928 was designed specifically for the
oncology setting, with a profile that includes potent activity in
the presence of high concentrations of adenosine and a minimal
shift in potency due to non-specific protein binding, both
essential properties to be efficacious in the tumor
microenvironment. AB928 has other attractive features, including
high penetration of tumor tissue and low penetration through the
healthy blood-brain barrier. In a Phase 1 trial in healthy
volunteers, AB928 has been shown to be safe and well tolerated and
to have pharmacokinetic and pharmacodynamic profiles consistent
with a once-daily dosing regimen.
About IPI-549 and the Ongoing Phase 1/1b Study
IPI-549 is an investigational
first-in-class, oral, immuno-oncology product candidate targeting
tumor-associated myeloid cells through selective
phosphoinositide-3-kinase-gamma (PI3K-gamma) inhibition, thereby
reducing pro-tumor macrophage function and increasing anti-tumor
macrophage function. In preclinical studies, IPI-549 demonstrated
the ability to reprogram macrophages from a pro-tumor (M2),
immune-suppressive function, to an anti-tumor (M1)
immune-activating function and enhance the activity of, and
overcome resistance to, checkpoint inhibitors.i
ii As such, IPI-549 may have the potential to treat a
broad range of solid tumors and represents a potentially additive
or synergistic approach to restoring anti-tumor immunity in
combination with other immunotherapies such as checkpoint
inhibitors.
The ongoing Phase 1/1b study being
conducted by Infinity is designed to evaluate the safety,
tolerability, activity, pharmacokinetics and pharmacodynamics of
IPI-549 as a monotherapy and in combination with
Opdivo® in approximately 200 patients with advanced
solid tumors.iii The study includes monotherapy and
combination dose-escalation components, in addition to monotherapy
expansion and combination expansion components. The monotherapy
dose-escalation and expansion components are complete. The
combination dose-escalation component is also complete, and
combination expansion cohorts are enrolling.
The combination expansion component of the study includes
multiple cohorts designed to evaluate IPI-549 in patients with
specific types of cancer, including patients with non-small cell
lung cancer (NSCLC), melanoma and head and neck cancer whose tumors
show initial resistance or initially respond to but subsequently
develop resistance to immune checkpoint blockade therapy. The
combination expansion component also includes a cohort of patients
with triple negative breast cancer (TNBC) who have not been
previously treated with immune checkpoint blockade therapy, a
cohort of patients with mesothelioma, a cohort of patients with
adrenocortical carcinoma and a cohort of patients with high
baseline blood levels of MDSCs.
About Arcus Biosciences
Arcus Biosciences is a
clinical-stage biopharmaceutical company focused on creating
innovative cancer immunotherapies. Arcus has several programs
targeting important immuno-oncology pathways, including a dual
adenosine receptor antagonist AB928, which will be evaluated in
combination with other agents in multiple tumor types in a Phase
1/1b program, and an anti-PD-1
antibody, which is being evaluated in a Phase 1 trial and will be
tested in combination with Arcus's other product candidates.
Arcus's other programs include a small molecule inhibitor of CD73
and an anti-TIGIT antibody, both of which are in IND-enabling
studies. Arcus has extensive in-house expertise in medicinal
chemistry, immunology, biochemistry, pharmacology and structural
biology. For more information about Arcus Biosciences, please
visit www.arcusbio.com.
About Infinity Pharmaceuticals
Infinity is an
innovative biopharmaceutical company dedicated to advancing novel
cancer treatments. Infinity is advancing IPI-549, a potentially
transformative immuno-oncology approach that aims to reprogram
tumor-associated macrophages by selectively inhibiting PI3K-gamma.
A Phase 1/1b study in approximately
200 patients with advanced solid tumors is ongoing. For more
information on Infinity, please refer to Infinity's website
at www.infi.com.
Arcus Forward-Looking Statements
This press release
contains forward-looking statements. All statements other than
statements of historical facts contained herein, including, but not
limited to, the potential of the triple combination therapies
in TNBC and ovarian cancers and timeline for topline data, are
forward-looking statements reflecting the current beliefs and
expectations of management made pursuant to the safe harbor
provisions of the Private Securities Litigation Reform Act of 1995.
All forward-looking statements involve known and unknown risks,
uncertainties and other important factors that may cause Arcus's
actual results, performance or achievements to differ significantly
from those expressed or implied. Factors that could cause or
contribute to such differences include, but are not limited to, the
inherent uncertainty associated with pharmaceutical product
development and clinical trials, delays in our clinical trials due
to difficulties or delays in the regulatory process, enrolling
subjects or manufacturing or supplying product for such clinical
trials, and the ability to demonstrate safety and activity of these
triple combinations in the four cohorts. Risks and uncertainties
facing Arcus are described more fully in Arcus's quarterly report
on Form 10-Q for the quarter ended March 31,
2018 filed on May 9, 2018 with
the SEC. You are cautioned not to place undue reliance on the
forward-looking statements, which speak only as of the date of this
press release. Arcus disclaims any obligation or undertaking to
update, supplement or revise any forward-looking statements
contained in this press release.
Infinity 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 therapeutic
potential of PI3K-gamma selective inhibition and IPI-549, alone and
in combination with one or more of Opdivo, AB928, AB122, and
chemotherapy, and plans to report topline data from the triple
combination studies. Management's expectations and such
forward-looking 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 the risks described under the caption "Risk
Factors" included in Infinity's quarterly report on Form 10-Q filed
with the Securities and Exchange Commission (SEC) on May
8, 2018, 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.
Arcus Biosciences Contact:
Jennifer Jarrett, 510-694-6261
jjarrett@arcusbio.com
or
Nicole Arndt, 510-284-4728
narndt@arcusbio.com
Infinity Pharmaceuticals Contact:
Daniella Funaro
Stern Investor Relations, Inc.
212-362-1200
daniella@sternir.com
i 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.
ii 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.
iii www.clinicaltrials.gov, NCT02637531.
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SOURCE Infinity Pharmaceuticals, Inc.; Arcus Biosciences