- AB928 was safe and well tolerated at all
doses evaluated -
- Safety and pharmacodynamic data from healthy
volunteer trial support selection of dose for evaluation of AB928
in combination with anti-PD-1 therapy in patients -
Arcus Biosciences, Inc. (NYSE:RCUS), a clinical-stage
biopharmaceutical company focused on creating innovative cancer
immunotherapies, today announced the final unblinded safety data
from its Phase 1 trial for AB928, its dual adenosine receptor
antagonist, in healthy volunteers. These results demonstrated that
AB928 was safe and well tolerated at all doses evaluated.
Pharmacokinetic and pharmacodynamic data from this trial were
previously presented in April at the 2018 American Association for
Cancer Research (AACR) Annual Meeting.
“We are pleased to see that AB928 was safe and well tolerated in
healthy volunteers, even at 200 mg once-daily, the highest dose
tested in the study. In addition, pharmacodynamic data from this
trial demonstrated that an AB928 dose between 75 mg and 150 mg
once-daily should be sufficient to achieve greater than 90%
inhibition of the adenosine 2a (A2a) receptor pathway,” said Joyson
Karakunnel, MD, MSc, FACP, Vice President of Clinical Development
at Arcus. “These results demonstrate that AB928 has an attractive
profile to be combined with standard-of-care regimens for the
treatment of cancer, such as anti-PD-1 antibodies or chemotherapy,
particularly in settings where adenosine is believed to play an
immuno-suppressive role. The results also support the selection of
the starting dose for the combination of AB928 and AB122, our
anti-PD-1 antibody, in patients.”
Design of the Phase 1 Trial for AB928 in Healthy
Volunteers
The Phase 1 double-blinded, randomized, placebo-controlled trial
enrolled 85 healthy volunteers. The trial included a
single-ascending-dose (SAD) portion and a multiple-ascending-dose
(MAD) portion. In the SAD portion, single doses of 10, 25, 75 and
150 mg and a twice-daily dose of 100 mg were evaluated. In the MAD
portion, once-daily doses of 10, 25, 75 and 150 mg and 200 mg (with
food) were administered to subjects for four consecutive days. In
each dosing cohort, six subjects received AB928 and two subjects
received placebo.
Summary of the Phase 1 Safety Results
- All reported adverse events (AEs) were
characterized as low-grade AEs (Grade 1 or Grade 2), with the
majority of the AEs being Grade 1 events.
- No AEs appeared to be dose dependent,
and no AEs prevented escalation to a higher dose.
- All treatment-related AEs were resolved
by the end of the study period, and no serious adverse events,
discontinuations or deaths were reported in the study.
- There were no variations in heart rate
or blood pressure that would not be considered within normal
parameters.
Based on the results from the healthy-volunteer trial, patients
in the first dose-escalation cohort for the Phase 1/1b program,
which will evaluate AB928 + AB122, will receive once-daily doses of
75 mg of AB928. The Company plans to present the final safety
results from the Phase 1 healthy-volunteer trial at a medical
conference later in the year.
About the Phase 1/1b Program for AB928
The Phase 1/1b program for AB928 is designed to evaluate the
safety and clinical activity of the combinations of AB928 + AB122
and AB928 + chemotherapy in selected tumor types characterized by
high levels of adenosine and / or CD73 as well as T cell
infiltration. These tumor types include triple negative breast
cancer, ovarian cancer, colorectal cancer, gastroesophageal cancer,
non-small cell lung cancer and renal cell carcinoma. As part of the
Phase 1/1b program, the Company also expects to evaluate the triple
combination of AB928 + anti-PD-1 therapy + chemotherapy in certain
settings such as non-small cell lung cancer. The Company plans to
present dose-escalation data for the combinations, including data
on safety, biomarker analysis and clinical activity, in the first
half of 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 for efficacy 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 AB122
AB122 is a fully human IgG4 antibody that potently and
selectively blocks PD-1. The biochemical, biological and
preclinical properties of AB122 have been shown to be similar to
those of the marketed anti-PD-1 antibodies nivolumab and
pembrolizumab. In August 2017, Arcus entered into a license
agreement with WuXi Biologics for an exclusive license to develop,
use, manufacture, and commercialize AB122 worldwide except for
China and five other countries outside of the U.S., Europe, Japan.
In November 2017, dosing was initiated in Australia for the Phase 1
trial of AB122 in cancer patients. The Company plans to report
initial data from this trial in the third quarter of 2018. The
Company expects AB122 to form the backbone of many of its
intra-portfolio combinations.
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 AB122, 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.
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 attractiveness of
AB928’s profile, its use in combination with other anti-cancer
agents and timelines for Arcus’s clinical programs, 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, the emergence of drug-related
adverse events in combination trials of AB928 and other anti-cancer
agents, delays in the company’s clinical trials due to difficulties
or delays in the regulatory process, enrolling subjects or
manufacturing or supplying product for such clinical trials, and
that the results of clinical trials may be subject to differing
interpretations. 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.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20180717005306/en/
Arcus BiosciencesJennifer Jarrett,
510-694-6261jjarrett@arcusbio.comorNicole Arndt,
510-284-4728narndt@arcusbio.com
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