Arcus Biosciences, Inc. (NYSE:RCUS), a clinical-stage
biopharmaceutical company focused on creating innovative cancer
immunotherapies, will present data today from its Phase 1 trial for
AB928, its dual adenosine receptor antagonist, in healthy
volunteers in a poster presentation titled “Clinical
Pharmacokinetic-Pharmacodynamic Relationship for AB928, a Dual
Antagonist of the A2aR and A2bR Adenosine Receptors,” at the 2018
American Association for Cancer Research (AACR) Annual Meeting in
Chicago, Illinois.
“We are extremely encouraged by the results from our ongoing
Phase 1 trial of AB928. The compound has been shown to be safe and
well tolerated at all doses evaluated and achieves near complete
inhibition of A2aR adenosine receptor activation in blood samples
from healthy volunteers,” said Terry Rosen, Ph.D., Chief Executive
Officer at Arcus. “Importantly, we achieved this level of
inhibition under conditions that we believe are representative of
the large concentrations of adenosine found in the tumor
microenvironment. These results have informed the selection of the
starting dose for our clinical trials of AB928 in combination with
other anti-cancer agents, and we look forward to starting these
trials shortly.”
Design of the Phase 1 Trial for AB928 in Healthy
Volunteers
The Phase 1 double-blinded, placebo-controlled trial has
enrolled 85 healthy volunteers. The trial includes a
single-ascending-dose (SAD) portion as well as 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
have been evaluated. In the MAD portion, doses of 10, 25, 75 and
150 mg QD and 200 mg QD (with food) have been administered to
subjects for four consecutive days. In each dosing cohort, 6
subjects received AB928 and 2 subjects received placebo, and dosing
in the trial has been completed. Investigators remain blinded
regarding subject assignment to the AB928 or placebo arms.
The objective of this trial is to assess the safety,
tolerability, pharmacokinetics and pharmacodynamic profile of AB928
and to inform our selection of the starting dose of AB928 for our
combination trials in cancer patients.
Summary of the Results Presented
All doses have been safe and well tolerated, and no safety
events prevented escalation to higher doses. To assess the
pharmacodynamic effects of AB928, blood samples were taken from
subjects at different time points following the administration of
AB928 or placebo. As of the cut-off date (COD) of March 30, 2018
for the poster presentation, samples from all dosing cohorts, with
the exception of the 200 mg QD (with food) MAD cohort, have been
evaluated to assess the pharmacodynamic effects of AB928. These
samples were treated with NECA (a synthetic analogue of adenosine),
which activates A2aR receptors on T cells. The ability of AB928 to
block A2aR receptors on T cells was quantified by measuring the
levels of pCREB, which is a marker for activation of the A2aR
receptor.
When blood samples from the 150 mg MAD cohort were incubated
with 5 µM NECA, AB928 achieved complete inhibition of pCREB
activation at two hours post-dosing and approximately 90% mean
inhibition of pCREB activation at 24 hours post-dosing on day 4. As
experiments conducted in vitro by Arcus have demonstrated that NECA
is at least 20 times more potent than adenosine at inducing pCREB
activation in blood T cells, stimulation with 5 µM NECA should be
comparable to stimulation with adenosine concentrations in excess
of 100 µM.
The pharmacokinetic profile of AB928 supports once-daily dosing,
with a plasma half-life that exceeds 20 hours.
Complete results from this trial, including pharmacodynamic data
for the 200 mg BID (with food) dosing cohort, will be released
following the unblinding of data in mid-2018.
AB928 Clinical Development Plans
The results from this healthy volunteer trial demonstrate that a
safe and well tolerated dose of AB928 can provide near complete
inhibition of A2aR receptor activation. Based on these results,
Arcus is preparing to initiate clinical trials to evaluate AB928 in
combination with three different chemotherapy regimens and in
combination with AB122, its PD-1 antibody, in cancer patients.
Regulatory submissions to start these trials are underway.
These trials will include a dose-escalation portion to identify
the recommended dose of AB928 for each combination regimen. Based
on the safety profile of AB928, the initial dose of AB928 for the
dose-escalation portion should achieve close to complete inhibition
of A2aR receptor activation. Once the recommended dose has been
selected, AB928 will be evaluated in 11 expansion cohorts. Each
expansion cohort will evaluate the AB928 + chemotherapy combination
and/or the AB928 + AB122 combination in one of the following tumor
types: non-small cell lung cancer, renal cell carcinoma,
gastroesophageal cancer, colorectal cancer, ovarian cancer and
triple negative breast cancer. In both the dose escalation portion
and expansion cohorts, Arcus will conduct significant biomarker
analysis, which will inform patient selection in future trials.
Arcus plans to report data from the dose-escalation portion of
these trials in the first half of 2019.
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 and an anti-PD-1
antibody, both of which are in Phase 1 trials, as well as a small
molecule inhibitor of CD73 and an anti-TIGIT antibody, 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 Statement
This press release contains forward-looking statements. All
statements other than statements of historical facts contained
herein, including, but not limited to, Arcus’s clinical
development plans, 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 applicability of the
results described herein to Arcus’s clinical development plans and
subsequent clinical trials; risks associated with preliminary data;
and 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. Risks and uncertainties
facing Arcus are described more fully in Arcus’s registration
statement on Form S-1 as filed 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.
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version on businesswire.com: https://www.businesswire.com/news/home/20180417005612/en/
Arcus Biosciences, Inc.Jennifer Jarrett,
510-694-6261jjarrett@arcusbio.comorNicole Arndt,
510-284-4728narndt@arcusbio.com
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