– IPI-549 with AB928 and AB122 in Triple Negative Breast Cancer
and Ovarian Cancer –
– IPI-549 with AB928 and Chemotherapy in Triple Negative Breast
Cancer and Ovarian Cancer –
HAYWARD, Calif. & CAMBRIDGE, Mass.--(BUSINESS WIRE)--
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.
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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.
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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Arcus Biosciences Contacts:
Jennifer Jarrett, 510-694-6261
jjarrett@arcusbio.com
or
Nicole
Arndt, 510-284-4728
narndt@arcusbio.com
or
Infinity
Pharmaceuticals Contact:
Stern Investor Relations, Inc.
Daniella
Funaro, 212-362-1200
daniella@sternir.com
Source: Arcus Biosciences