HAYWARD, Calif.--(BUSINESS WIRE)--
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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Arcus Biosciences, Inc.
Jennifer Jarrett, 510-694-6261
jjarrett@arcusbio.com
or
Nicole
Arndt, 510-284-4728
narndt@arcusbio.com
Source: Arcus Biosciences, Inc.