Aclaris Therapeutics, Inc. (NASDAQ: ACRS), a clinical-stage
biopharmaceutical company focused on developing novel drug
candidates for immuno-inflammatory diseases, today announced
positive preliminary topline results from a 12-week, Phase 2a,
multicenter, randomized, investigator and patient-blind,
sponsor-unblinded, parallel group, placebo-controlled clinical
trial to investigate the safety, tolerability, pharmacokinetics and
pharmacodynamics of ATI-450, an investigational oral MK2 inhibitor,
in subjects with moderate to severe rheumatoid arthritis (RA)
(ATI-450-RA-201). ATI-450 was developed internally utilizing
Aclaris’ proprietary KINect™ drug discovery platform.
In the trial, 19 subjects were randomized in a 3:1 ratio and
received either ATI-450 at 50 mg twice daily or placebo, in
combination with methotrexate, for 12 weeks. The primary endpoint
was safety and tolerability. Key secondary and exploratory
endpoints included the disease activity scores, DAS28-CRP and
ACR20/50/70, and the change from baseline in high sensitivity
C-reactive protein (hsCRP) and relevant endogenous cytokine levels.
As this trial was designed to generate proof of concept, it was not
powered to detect statistically significant outcomes on efficacy
endpoints.
The mean DAS28-CRP score at baseline was 5.71 for the 16
subjects in the treatment arm and 5.77 for the three subjects in
the placebo arm. Seventeen subjects (15 in the treatment arm and
two in the placebo arm) completed 12 weeks of treatment.
In this trial, ATI-450 demonstrated durable clinical activity,
as defined by a marked and sustained reduction in DAS28-CRP and
evaluation of ACR20/50/70 responses over 12 weeks. The mean change
from baseline in DAS28-CRP score at week 12 was a 2.0 reduction in
the treatment arm compared to a 0.35 increase in the placebo arm.
The proportion of subjects with a DAS28-CRP score at week 12 of ≤
3.2 (low disease activity or remission) was 40% and 0% in the
treatment and placebo arms, respectively, and the proportion of
subjects with a DAS28-CRP score of < 2.6 (remission) was 20% and
0% in the treatment and placebo arms, respectively.
ACR20/50/70 was observed at week 12 in 60%, 33% and 20%,
respectively, of the 15 subjects in the treatment arm, and in 0% of
the two subjects in the placebo arm. The median reduction from
baseline in hsCRP was >40% throughout the 12 weeks of the trial
in the treatment arm. A sustained median reduction from baseline in
hsCRP was not observed in the placebo arm. An interim analysis (11
treatment, two placebo) of ex vivo stimulated cytokines from blood
samples taken from the treatment arm showed a marked and durable
inhibition of TNFα, IL1β, IL6, and IL8 over the 12 week dosing
period. Similarly, analysis of endogenous cytokines also
demonstrated a marked and sustained inhibition of median
concentrations of TNFα, IL6, IL8, and MIP1β in the treatment arm
over the 12 week period.
ATI-450 was generally well tolerated. No serious adverse events
were reported and all adverse events were mild to moderate. The
most common adverse events (each reported in 2 subjects) were
urinary tract infection (UTI), elevated lipids and ventricular
extrasystoles, all of which were determined to be unrelated to
treatment except for one UTI. Two subjects withdrew from the trial,
one in the treatment arm and one in the placebo arm.
ATI-450 was also evaluated at higher doses in a separate Phase 1
clinical trial in healthy subjects (ATI-450-PKPD-102). In this
placebo-controlled Phase 1 trial, one group of healthy subjects
received 80 mg of ATI-450 twice daily and another group of healthy
subjects received 120 mg of ATI-450 twice daily over 6.5 days. No
dose-limiting toxicity was observed. Ex vivo analysis of blood
samples from this Phase 1 trial showed that increased cytokine
inhibition was achieved with these higher doses of ATI-450. A final
analysis of this trial is underway.
Dr. David Gordon, Chief Medical Officer of Aclaris, said, “We’re
very pleased with these data which demonstrate that ATI-450 was
generally well tolerated and showed durable clinical activity in RA
over 12 weeks. We believe these data support our hypothesis that
MK2 inhibition is an important novel target for the treatment of
immuno-inflammatory diseases, such as rheumatoid arthritis, and we
look forward to progressing ATI-450 to Phase 2b. We want to thank
everyone who participated in these informative trials.”
“Despite recent advances, rheumatoid arthritis continues to be a
significant burden for large numbers of patients,” said Stanley
Cohen, MD, Clinical Professor in the Department of Internal
Medicine and a Clinical Faculty Member in the Division of
Rheumatology at UT Southwestern Medical School, and a Co-Director
of the Division of Rheumatology at Presbyterian Hospital, Dallas.
“These results are very encouraging and support further development
of ATI-450 to treat rheumatoid arthritis with a new mechanism of
action.”
Aclaris expects to submit a full analysis of the Phase 2a data
for publication in a peer-reviewed scientific journal. The full
analysis will include data from other secondary and exploratory
endpoints evaluated in the trial, including the four-week safety
follow-up data and a full analysis of MRI, pharmacodynamic and
pharmacokinetic data.
Conference Call and Webcast
Management will host a conference call and webcast with an
accompanying slide presentation at 8:00 AM ET today to review these
preliminary topline Phase 2a data and related matters. To
participate in the live call, please dial (844) 776-7782 (domestic)
or (661) 378-9535 (international) and reference conference ID
7166952. To access the live webcast of the call and the
accompanying slide presentation, please visit the “Events” page of
the “Investors” section of Aclaris’ website, www.aclaristx.com. The
webcast will be archived for at least 30 days on the Aclaris
website.
About ATI-450
ATI-450 is an investigational oral mitogen-activated protein
kinase-activated protein kinase 2 (MK2) inhibitor. This mechanism
potentially 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.
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 RA, the clinical development of ATI-450, including the further
development at higher doses, and the publication of the full
analysis from the ATI-450-RA-201 trial. 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,
risks and uncertainties associated with preliminary trial results
varying from final results, 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
September 30, 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 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
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