SAN JOSE, Calif., Sept. 3, 2019 /PRNewswire/ -- Aridis
Pharmaceuticals, Inc. (Nasdaq: ARDS), a biopharmaceutical
company focused on the discovery and development of novel
anti-infective therapies to treat life-threatening bacterial
infections, today announced results from the Company's
first-in-patient Phase 2 clinical trial evaluating AR-105, a fully
human IgG1 monoclonal antibody for the treatment of
ventilator-associated pneumonia (VAP) caused by gram-negative
Pseudomonas aeruginosa (P. aeruginosa). The recently
completed study did not meet its primary endpoint of demonstrating
superiority in Clinical Cure rates on Day 21 compared to
placebo. Furthermore, there was a statistically significant
imbalance in all-cause mortality, as well as Serious Adverse Event
(SAE) rates between treatment groups that favored placebo. However,
no SAE or mortality in the study was deemed to be drug related by
the study investigators or the study's Data Monitoring Committee.
At this point, the Company will no longer allocate further
development resources to AR-105.
"Our team is analyzing the full data set to better understand
these top-line results and report the final analysis as soon as
possible. We wish to extend our appreciation to the patients, their
families, and investigators for their contribution to the study,"
commented Wolfgang Dummer, M.D.,
Ph.D., Chief Medical Officer of Aridis Pharmaceuticals.
"I want to underscore our gratitude for efforts of the
investigators, patients, and families from which a substantial body
of data has been generated that will guide further development of
anti-infective immunotherapies," commented Vu Truong, Ph.D., Chief Executive Officer of
Aridis Pharmaceuticals. "Moving forward, we remain
enthusiastic about and will re-focus on the balance of our robust
pipeline including AR-301 and AR-501 which are both in clinical
development. Our lead antibody, AR-301, targets
gram-positive S. aureus alpha-toxin and is
currently in Phase 3 global clinical development for the treatment
of VAP. This trial is progressing on track, and we look forward to
reporting interim data in the first half of 2020 as well as the
subsequent top-line data in late 2020."
The AR-301 Phase 3 trial, which was initiated in the first
quarter of 2019, is actively enrolling in approximately 240
clinical centers in 20 countries. Participating centers in all
countries are following a single stringent clinical protocol and
standard of care procedures for critically ill VAP patients. The
trial represents the first ever Phase 3 superiority clinical study
evaluating immunotherapy with a fully human monoclonal antibody for
the treatment of acute pneumonia in the intensive care unit (ICU)
setting. Details of the study can be viewed
on www.clinicaltrials.gov using identifier
NCT03816956.
AR-301 is a fully human monoclonal IgG1 antibody that was
derived from our proprietary MabIgX® platform technology,
specifically targeting gram-positive S.
aureus alpha-toxin, which is a secreted toxin well-known
as being central and indispensable to the pathogenesis of this
bacteria. It has been shown in vitro to protect against
alpha-toxin mediated destruction of host cells, thereby potentially
preserving the human immune response. AR-301's anti-toxin target
and mode of action are different from AR-105's cell surface
carbohydrate target and mode of action, and is independent of the
antibiotic resistance profile of S.
aureus. Additional external validation of targeting S.
aureus alpha-toxin has also been obtained from AstraZeneca's
MEDI-4893, another monoclonal antibody against this epitope, which
is in development for the prophylaxis of S. aureus VAP.
The Company also remains on track with its AR-501 program, an
inhaled formulation of gallium citrate being developed as a
non-antibiotic anti-infective to treat lung infections in cystic
fibrosis patients, with top-line data from its Phase 1/2a clinical
trial in healthy subjects and cystic fibrosis patients. The data
from the healthy subjects is expected by the end of Q1 2020 and
from cystic fibrosis patients in Q2 2021. External validation of
successful treatment of cystic fibrosis patients with an
intravenous formulation of gallium was reported recently from a
Phase 2 clinical study conducted by the University of Washington with an acceptable safety
profile and statistically significant improvement in lung
function.
Additionally, the Company continues to utilize its
proprietary MabIgX® technology platform to rapidly identify
rare, potent antibody-producing B-cells from patients to develop
new anti-infective monoclonal antibodies.
About AR-105
The development of AR-105, a mAb
targeting a cell surface carbohydrate (alginate) on P.
aeruginosa, was based on animal models of acute pneumonia,
sepsis and keratitis which supported its usage as both a
therapeutic and prophylactic therapy. Focusing on AR-105's
therapeutic use, a Phase 1 dose-ranging, clinical trial was
conducted involving 16 healthy adult volunteers who received up to
a 20 mg/kg IV dose of this agent. In this study, AR-105 was shown
to be safe and well tolerated and exhibited a plasma half-life of
approximately 21 days. This trial informed the choice of both the
dose (20 mg/kg) and schedule (one IV injection) for the Phase 2-
trial.
The Phase 2 trial (ClinicalTrials.gov Identifier: NCT03027609),
which was initiated in the second quarter of 2017, was a
randomized, double blinded, placebo controlled, superiority study
which treated 158 VAP patients in 53 clinical sites from 13
countries across the U.S., Europe
and Asia. Patient enrollment was
based on admittance to an intensive care unit for pneumonia caused
by P. aeruginosa bacteria as determined using a rapid
diagnostic and/or culture test. Such VAP patients were randomized
in a 1:1 fashion to receive either standard-of-care antibiotic
therapy with placebo (placebo arm) or standard-of-care antibiotic
therapy in addition to AR-105 (experimental arm). The treatment
regimen was a single intravenous infusion (IV) of either AR-105 at
a dose of 20 mg/kg or placebo. The primary endpoint of this trial
was clinical cure of pneumonia at Day 21 post study drug treatment,
as determined by the principal investigator. The trial was designed
to demonstrate statistical superiority of AR-105 over
standard-of-care. Secondary endpoints of the trial included
clinical cure of pneumonia at Day 28, Day 14, or Day 7, all-cause
mortality, and several health economics parameters.
About Aridis Pharmaceuticals, Inc.
Aridis
Pharmaceuticals, Inc. discovers and develops anti-infectives to be
used as add-on treatments to standard-of-care antibiotics. The
Company is utilizing its proprietary MabIgX® technology platform to
rapidly identify rare, potent antibody-producing B-cells from
patients who have successfully overcome an infection to produce
mAbs. These mAbs are already of human origin and functionally
optimized for high potency by the donor's immune system; hence,
they do not require genetic engineering or further optimization to
achieve full functionality. MabIgX® also allows for the selection
of any antibody isotype depending on the optimal effector function
required for treating the target infection. By bypassing the
humanization and binding sequence optimization steps, and the
entire process of generation of genetically engineered antibody
producing cell lines, MabIgX® enables high gross-margins and
expedited progression to clinical development.
The Company has generated multiple clinical stage mAbs targeting
bacteria that cause life-threatening infections such as
VAP and HAP. The use of mAbs as anti-infective treatments
represents an innovative therapeutic approach that harnesses the
human immune system to fight infections and is designed to overcome
the deficiencies associated with the current standard of care which
is broad spectrum antibiotics. Such deficiencies include, but are
not limited to, increasing drug resistance, short duration of
efficacy, disruption of the normal flora of the human microbiome
and lack of differentiation among current treatments. The mAb
portfolio is complemented by a non-antibiotic novel mechanism small
molecule anti-infective candidate being developed to treat lung
infections in cystic fibrosis patients. The company's pipeline is
highlighted below:
Aridis' Pipeline
AR-301 (VAP). AR-301
is a fully human immunoglobulin 1, or IgG1, mAb currently in Phase
3 clinical development targeting gram-positive S.
aureus alpha-toxin in VAP patients.
AR-101 (HAP). AR-101 is a fully human
immunoglobulin M, or IgM, mAb targeting P.
aeruginosa liposaccharides serotype O11, which accounts
for approximately 22% of all P.
aeruginosa hospital acquired pneumonia cases
worldwide.
AR-501 (cystic fibrosis). AR-501 is an inhaled
formulation of gallium citrate with broad-spectrum anti-infective
activity being developed to treat chronic lung infections in cystic
fibrosis patients. This program is currently in a Phase 1/2a
clinical study in healthy volunteers and CF patients.
AR-401 (blood stream infections). AR-401 is a
fully human mAb preclinical program aimed at treating infections
caused by gram-negative Acinetobacter baumannii.
AR-201 (RSV infection). AR-201 is a fully human IgG1
mAb preclinical program aimed at neutralizing diverse clinical
isolates of respiratory syncytial virus (RSV).
For additional information on Aridis Pharmaceuticals, please
visit https://aridispharma.com/.
Forward-Looking Statements
Certain statements in this
press release are forward-looking statements that involve a number
of risks and uncertainties. These statements may be
identified by the use of words such as "anticipate," "believe,"
"forecast," "estimated" and "intend" or other similar terms or
expressions that concern Aridis' expectations, strategy, plans or
intentions. These forward-looking statements are based on Aridis'
current expectations and actual results could differ materially.
There are a number of factors that could cause actual events
to differ materially from those indicated by such forward-looking
statements. These factors include, but are not limited to,
the timing of regulatory submissions, Aridis' ability to obtain and
maintain regulatory approval of its existing product candidates and
any other product candidates it may develop, approvals for clinical
trials may be delayed or withheld by regulatory agencies, risks
relating to the timing and costs of clinical trials, risks
associated with obtaining funding from third parties, management
and employee operations and execution risks, loss of key personnel,
competition, risks related to market acceptance of products,
intellectual property risks, risks associated with the uncertainty
of future financial results, Aridis' ability to attract
collaborators and partners and risks associated with Aridis'
reliance on third party organizations. While the list of
factors presented here is considered representative, no such list
should be considered to be a complete statement of all potential
risks and uncertainties. Unlisted factors may present significant
additional obstacles to the realization of forward-looking
statements. Actual results could differ materially from those
described or implied by such forward-looking statements as a result
of various important factors, including, without limitation, market
conditions and the factors described under the caption "Risk
Factors" in Aridis' 10-K for the year ended December 31, 2018 and Aridis' other filings
made with the Securities and Exchange
Commission. Forward-looking statements included herein are
made as of the date hereof, and Aridis does not undertake any
obligation to update publicly such statements to reflect subsequent
events or circumstances.
Contact:
Investor Relations
Jason Wong
Blueprint Life Science Group
jwong@bplifescience.com
(415) 375-3340 Ext. 4
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SOURCE Aridis Pharmaceuticals, Inc.