Pliant Therapeutics Presentations at The Liver Meeting® 2023 Highlight Bexotegrast, an Inhibitor of αvß6 and αvß1 Integrins, in Primary Sclerosing Cholangitis
13 Noviembre 2023 - 3:30PM
Pliant Therapeutics, Inc. (Nasdaq: PLRX), a clinical-stage
biotechnology company and leader in the discovery and development
of novel therapeutics for the treatment of fibrotic diseases, today
announced the presentation of preclinical data and clinical data
from the INTEGRIS-PSC Phase 2a trial of bexotegrast in patients
with primary sclerosing cholangitis (PSC). These posters were
presented at The Liver Meeting® 2023 of the American Association
for the Study of Liver Diseases (AASLD). The meeting is being held
November 10-14, 2023.
“Our presentations at the Liver Meeting feature preclinical and
clinical work supportive of bexotegrast’s antifibrotic mechanism of
action in liver fibrosis,” said Éric Lefebvre, M.D., Chief Medical
Officer of Pliant. “A highlight of the conference was the
late-breaker presentation of our recent positive interim data from
the INTEGRIS-PSC trial, demonstrating the potential of bexotegrast
in the unmet area of need of patients with PSC.”
Late Breaker: Oral
αvβ6/αVβ1
Integrin Inhibition in Primary Sclerosing Cholangitis:
12-week Interim Safety and Efficacy Analysis of INTEGRIS-PSC, A
Phase 2a Trial of Bexotegrast
Professor Gideon Hirschfield, M.D., Lily and Terry Horner Chair
in Autoimmune Liver Disease Research, Toronto Centre for Liver
Disease and INTEGRIS-PSC trial investigator presented interim data
from the 40, 80, 160 mg dose cohorts from INTEGRIS-PSC, an ongoing,
double-blind, dose-ranging, randomized, placebo-controlled Phase 2a
trial of bexotegrast in participants with PSC. Bexotegrast was well
tolerated over 12 weeks of treatment with no treatment-related
severe or serious treatment emergent adverse events. At all doses
tested, bexotegrast reduced changes in enhanced liver fibrosis
(ELF) score and PRO-C3 levels from Baseline relative to placebo,
with statistically significant differences for both parameters
observed with the 160 mg dose. Twelve-week data from the
INTEGRIS-PSC 320mg cohort is expected in the first quarter of
2024.
Inhibition of Integrin αVβ1 Attenuates Profibrogenic
Gene Expression by Myofibroblasts in Fibrotic Human Liver
Explants
An αVβ1-selective integrin inhibitor was evaluated on fibrotic
and non-fibrotic human liver tissue to assess the effects on cell
populations present in fibrotic human liver tissue. The αVβ1
integrin is a (myo)fibroblast-specific integrin that activates
transforming growth factor (TGF)-β that promotes fibrogenesis, or
wound healing and repair. Results showed that treatment of fibrotic
human tissue with an αVβ1 inhibitor resulted in clear reductions in
profibrogenic gene expression by myofibroblasts. In addition, αVβ1
and ALK5 (TGF-β receptor) inhibitors demonstrated similar effects
on fibrogenic gene expression in myofibroblasts highlighting the
significance of the αVβ1 integrin-TGF-β activation pathway in
fibrotic liver disease.
Dual
αVβ6/αVβ1
Integrin Inhibitor Bexotegrast Attenuates Profibrogenic
Gene Expression Across Multiple Pathologic Cell Types in Human
Liver Explant Tissue with Biliary Fibrosis
The effects of bexotegrast (PLN-74809), a dual inhibitor of
integrins αVβ6 and αVβ1, were assessed on human liver tissue to
characterize the response of unique cell populations in fibrotic
primary sclerosing cholangitis (PSC) and primary biliary
cholangitis (PBC). Treatment with bexotegrast was shown to
significantly decrease profibrogenic pathways in myofibroblasts and
reduce gene expression in scar-associated endothelial cells. In
addition, bexotegrast’s anti-fibrotic effect was similar to ALK5i
(TGF-β receptor inhibitor) demonstrating the importance the
αvβ6/αvβ1 integrin-TGF-β activation pathway in fibrotic biliary
disease. These data support the ongoing clinical study evaluating
the anti-fibrotic activity of bexotegrast in PSC.
These posters and the late breaker presentation are also
available on the Publications page of the Pliant’s website at
www.PliantRx.com.
About Pliant Therapeutics, Inc.
Pliant Therapeutics is a clinical-stage biopharmaceutical
company and leader in the discovery and development of novel
therapeutics for the treatment of fibrotic diseases. Pliant's lead
product candidate, bexotegrast (PLN-74809), is an oral, small
molecule, dual selective inhibitor of αvß6 and αvß1 integrins that
is in development in the lead indications for the treatment of
idiopathic pulmonary fibrosis, or IPF, and primary sclerosing
cholangitis, or PSC. Bexotegrast has received Fast Track
Designation and Orphan Drug Designation from the U.S. Food and Drug
Administration (FDA) in IPF and PSC and Orphan Drug Designation
from the European Medicines Agency in IPF and PSC. Pliant has
initiated BEACON-IPF, a Phase 2b trial of bexotegrast in IPF.
Pliant has also developed PLN-1474, a small molecule, selective
inhibitor of αvß1 integrin for the treatment of nonalcoholic
steatohepatitis, or NASH with liver fibrosis. Pliant has initiated
a Phase 1 study for its third clinical program, PLN-101095, a small
molecule, dual-selective inhibitor of αvß8 and αvß1 integrins, that
is being developed for the treatment of solid tumors. In addition
to clinical-stage programs, Pliant currently has a preclinical
program targeting muscular dystrophies. For additional information,
please visit: www.PliantRx.com. Follow us on social media
X, LinkedIn, Facebook and YouTube.
Forward-Looking Statements
Statements contained in this press release regarding matters
that are not historical facts are "forward-looking statements"
within the meaning of the Private Securities Litigation Reform Act
of 1995. Words such as "may," "will," "expect," "anticipate,"
"estimate," "intend," and similar expressions (as well as other
words or expressions referencing future events, conditions, or
circumstances) are intended to identify forward-looking statements.
These statements include those regarding the safety, tolerability,
pharmacodynamics and therapeutic potential of bexotegrast; our
plans for the future development of bexotegrast; bexotegrast’s
potential to become a treatment for IPF or PSC; the anticipated
timing of data and progress from our clinical studies; including
the timing of 12-week and 24-week data from the 320 mg dose cohort
of the INTEGRIS-PSC Phase 2a trial in the first quarter of 2024 and
mid-2024, respectively. Because such statements deal with future
events and are based on our current expectations, they are subject
to various risks and uncertainties and actual results, performance
or achievements of Pliant Therapeutics could differ materially from
those described in or implied by the statements in this press
release. These forward-looking statements are subject to risks and
uncertainties, including those related to the development and
commercialization of our product candidates, including any delays
in our ongoing or planned preclinical or clinical trials, the
impact of current macroeconomic and marketplace conditions, our
reliance on third parties for critical aspects of our development
operations, the risks inherent in the drug development process, the
risks regarding the accuracy of our estimates of expenses and
timing of development, our capital requirements and the need for
additional financing, including the availability of additional term
loans under our loan facility, and our ability to obtain and
maintain intellectual property protection for our product
candidates. These and additional risks are discussed in the
sections titled "Risk Factors" and "Management's Discussion and
Analysis of Financial Condition and Results of Operations" in our
Quarterly Report on Form 10-Q for the period ended June 30, 2023
which is available on the SEC's website at www.sec.gov. Unless
otherwise noted, Pliant is providing this information as of the
date of this news release and does not undertake any obligation to
update any forward-looking statements contained in this document as
a result of new information, future events or otherwise.
Investor and Media Contact:
Christopher KeenanVice President, Investor Relations and
Corporate CommunicationsPliant Therapeutics,
Inc.ir@pliantrx.com
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