Aclaris Therapeutics Supports Investigator-Initiated Clinical Trial of ATI-450 for Cytokine Release Syndrome in Hospitalized ...
June 17 2020 - 7:01AM
Aclaris Therapeutics, Inc. (NASDAQ: ACRS), a clinical-stage
biopharmaceutical company developing a pipeline of novel drug
candidates for immuno-inflammatory diseases, today announced that
the FDA has allowed an investigational new drug application to
evaluate ATI-450, its oral investigational MK2 inhibitor compound,
in hospitalized patients with COVID-19. Aclaris is supporting
an investigator-initiated trial of ATI-450 for cytokine release
syndrome (CRS) in 36 hospitalized patients with COVID-19, and will
provide funding and clinical drug supply to the University of
Kansas Medical Center (KUMC), the sponsor of the trial. The trial
will be led by co-investigators Gregory Gan, M.D., Ph.D. and
Deepika Polineni, M.D., M.P.H. The trial is a Phase 2a, randomized,
double-blind, placebo-controlled trial to investigate the safety
and efficacy of ATI-450, when used in addition to standard of care
therapy. The primary endpoint is the proportion of subjects who are
free from respiratory failure by day 14.
“CRS leads to the release of multiple inflammatory cytokines
such as IL1β, IL6 and TNFα, which precedes acute
respiratory distress syndrome, and is associated with significant
morbidity and mortality in patients with COVID-19. ATI-450, a novel
oral compound, has demonstrated that it targets the expression of
inflammatory cytokines in a Phase 1 clinical trial in healthy
volunteers. Therefore, we believe that ATI-450 may be an innovative
approach to managing this disease,” said Dr. Gan. As further noted
by Dr. Polineni, “By mitigating CRS, important clinical outcomes
such as oxygenation in patients with COVID-19 would be improved
which could result in the reduced need for ventilation in patients
in the intensive care setting.”
ATI-450 has been observed to regulate pro-inflammatory cytokines
associated with CRS. Pharmacodynamic analysis from the
first-in-human study using an ex vivo lipopolysaccharide (LPS)
stimulation model demonstrated dose-dependent reduction of TNFα,
IL1β, IL6 and IL8. Further analysis using this LPS
model showed marked inhibition of additional cytokines linked to
CRS, including GM-CSF, IL2, IFNγ and MIP1α. Furthermore,
anti-inflammatory activity for ATI-450 was observed in a rat model
of airway neutrophilia induced by inhaled LPS. In addition,
anti-viral1,2,3 and anti-fibrotic4,5 activity has been observed
following blockade of the MK2 pathway in preclinical studies.
“Many of the investigational drugs that are being evaluated to
treat CRS target a single cytokine,” said Dr. David Gordon, Chief
Medical Officer of Aclaris. “We believe inhibiting multiple
cytokines has the potential to achieve clinical benefits in
patients with CRS, and this study will explore if ATI-450 is an
effective approach in these patients. Thanks to KUMC, who are
sponsoring this trial, we are able to evaluate ATI-450 as a
potential treatment for COVID-19 at this critical time without
impacting our ongoing clinical development programs. If successful,
we hope to further explore the role that ATI-450 may have in
helping patients with COVID-19 and addressing the healthcare
challenges of the pandemic.”
Company to Host Conference Call
Management will conduct a conference call at 8:30 AM ET today to
discuss this trial and related matters. The conference call
will be webcast live over the Internet and can be accessed through
the Events page under the Investors section of Aclaris’ website,
www.aclaristx.com. A replay of the webcast will be archived on the
Aclaris website for 30 days following the call.
To participate on the live call, please dial (844)
776-7782 (domestic) or (661) 378-9535 (international), and
reference conference ID 1366937 prior to the start of the
call.
About COVID-19
Coronavirus disease 2019 (COVID-19) is a new pandemic disease
caused by the severe acute respiratory syndrome coronavirus 2
(SARS-CoV-2). Some patients require hospitalization, mostly due to
pneumonia, and can progress quickly to severe acute lung injury and
acute respiratory distress syndrome (ARDS), which is associated
with high mortality.6,7 A viral-induced cytokine storm or
“hyperimmune response” is hypothesized to be a major pathogenic
mechanism of ARDS.8,9,10
About ATI-450
ATI-450 is an investigational oral mitogen-activated protein
kinase-activated protein kinase 2 (MK2) inhibitor in Phase 2
clinical development. This mechanism leads to the inhibition of
multiple cytokines, chemokines, matrix metalloproteases and other
inflammatory signals. Key inflammatory cytokines driven by this
mechanism include tumor necrosis factor α (TNFα) and
interleukin-1α, -1β, -6 and -8 (IL1α, IL1β, IL6 and IL8). Aclaris
is developing ATI-450 as a potential treatment for rheumatoid
arthritis and other immuno-inflammatory diseases.
About Aclaris Therapeutics,
Inc.
Aclaris Therapeutics, Inc. is a clinical-stage biopharmaceutical
company developing a pipeline of novel drug candidates to address
the needs of patients with immuno-inflammatory diseases who lack
satisfactory treatment options. The company has a multi-stage
portfolio of drug candidates powered by a robust R&D engine
exploring protein kinase regulation. For additional information,
please visit www.aclaristx.com and follow Aclaris on LinkedIn or
Twitter @aclaristx.
Cautionary Note Regarding Forward-Looking
Statements
Any statements contained in this press release that do not
describe historical facts may constitute forward-looking statements
as that term is defined in the Private Securities Litigation Reform
Act of 1995. These statements may be identified by words such as
“believe,” “expect,” “intend,” “may,” “plan,” “potential,” “will,”
and similar expressions, and are based on Aclaris’ current beliefs
and expectations. These forward-looking statements include
expectations regarding ATI-450 as a potential treatment
for patients with COVID-19 and the clinical development of ATI-450.
These statements involve risks and uncertainties that could cause
actual results to differ materially from those reflected in such
statements. Risks and uncertainties that may cause actual results
to differ materially include uncertainties inherent in the conduct
of clinical trials, Aclaris’ reliance on third parties over which
it may not always have full control, Aclaris’ ability to enter into
strategic partnerships on commercially reasonable terms, the
uncertainty regarding the COVID-19 pandemic and other risks and
uncertainties that are described in the Risk Factors section of
Aclaris’ Annual Report on Form 10-K for the year ended December 31,
2019, Aclaris’ Quarterly Report on Form 10-Q for the quarter ended
March 31, 2020, and other filings Aclaris makes with the U.S.
Securities and Exchange Commission from time to time. These
documents are available under the “SEC filings” page of the
Investors section of Aclaris’ website at http://www.aclaristx.com.
Any forward-looking statements speak only as of the date of this
press release and are based on information available to Aclaris as
of the date of this release, and Aclaris assumes no obligation to,
and does not intend to, update any forward-looking statements,
whether as a result of new information, future events or
otherwise.
Aclaris Contact
investors@aclaristx.com
References
- McCaskill JL, Ressel S, Alber A, et al. Broad-Spectrum
Inhibition of Respiratory Virus Infection by MicroRNA Mimics
Targeting p38 MAPK Signaling. Mol Therapy: Nuc Acids.
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- Luig C, Köther K, Dudek SE, et al. MAP kinase-activated protein
kinases 2 and 3 are required for influenza A virus propagation and
act via inhibition of PKR. FASEB J. 2010;24:4068-4077.
- Jimenez-Guardeño JM, Nieto-Torres JL, DeDiego ML, et al. The
PDZ-Binding Motif of Severe Acute Respiratory Syndrome Coronavirus
Envelope Protein Is a Determinant of Viral Pathogenesis. PLoS
Pathog. 2014;10(8):1-20.
- Liang J, Liu N, Liu X, et al. Mitogen-activated Protein
Kinase–activated Protein Kinase 2 Inhibition Attenuates Fibroblast
Invasion and Severe Lung Fibrosis. Am J Respir Cell Mol Biol.
2019;60(1):41–48.
- Vittal R, Fisher A, Gu H, et al. Peptide-Mediated Inhibition of
Mitogen-Activated Protein Kinase–Activated Protein Kinase–2
Ameliorates Bleomycin-Induced Pulmonary Fibrosis. Am J Respir Cell
Mol Biol. 2013;49(1):47–57.
- Huang C, Wang Y, Li X, et al. Clinical features of patients
infected with 2019 novel coronavirus in Wuhan, China. Lancet.
2020;395:497-506.
- Zhou F, Yu T, Du R, et al. Clinical course and risk factors for
mortality of adult inpatients with COVID-19 in Wuhan, China: a
retrospective cohort study. Lancet. 2020;395:1054-1062.
- Mehta P, McAuley DF, Brown M, et al. COVID-19: consider
cytokine storm syndromes and immunosuppression. Lancet.
2020;395:1033-1034.
- Moore, JB, June CH. Cytokine release syndrome in severe
COVID-19. Science. 2020;368(6490):473-474.
- Zhang C, Wu Z, Li JW, et al. Cytokine release syndrome in
severe COVID-19: interleukin-6 receptor antagonist tocilizumab may
be the key to reduce mortality. Int. J. Antimicrob. Agents.
2020;55(5):1-6.
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