PureTech Announces Publication of Glyph™ Platform Preclinical Proof-of-Concept Study in Journal of Controlled Release
25 Febrero 2021 - 8:17AM
Business Wire
Publication demonstrates the ability to
directly target gut lymphatics with an orally dosed small molecule
immunomodulator
First product candidate from Glyph platform,
LYT-300 (oral allopregnanolone), expected to enter clinical trial
by the end of 2021
PureTech Health plc (Nasdaq: PRTC, LSE: PRTC) (“PureTech” or the
“Company”), a clinical-stage biotherapeutics company dedicated to
discovering, developing and commercializing highly differentiated
medicines for devastating diseases, today announced the publication
of a research paper in the Journal of
Controlled Release. Results provide further preclinical
proof-of-concept for PureTech’s Glyph platform technology, which is
designed to traffic small molecule therapeutics directly into the
lymphatic system via oral administration.
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PureTech announced the publication of a
paper in the Journal of Controlled Release. Results provide further
preclinical proof-of-concept for PureTech’s lymphatic targeting
technology platform Glyph, which is designed to traffic small
molecule therapeutics directly into the lymphatic system via oral
administration. (Graphic: Business Wire)
Results highlighted in the publication demonstrate the ability
of a therapeutic modality built from PureTech’s Glyph platform to
target administration of mycophenolic acid (MPA), an
immunosuppressant, into lymph and directly into gut-draining
mesenteric lymph nodes (MLNs). As a key nexus of immune cell
trafficking, MLNs play major roles in the pathophysiology of a
range of conditions including inflammatory and autoimmune diseases,
cancer, and metabolic diseases.
“The Glyph platform has tremendous therapeutic potential for
orally administered medicines because it may allow us to bypass
first-pass metabolism in the liver and directly target the
lymphatic system, which is a critical site for immune cell
programming and trafficking. With this study, we have shown that
the platform enhances immunomodulation in the mesenteric lymph
nodes,” said Christopher Porter, Ph.D., Director of the Monash
Institute of Pharmaceutical Sciences at Monash University in
Melbourne, lead author of the study and a PureTech collaborator.
“This in vivo proof of concept is an excellent foundation for
advancing drug development that leverages the Glyph platform.”
As published, oral administration of a Glyph-derived prodrug of
MPA resulted in a >80-fold increase in uptake of total MPA into
the lymphatic system and a >20-fold increase in MPA
concentrations in MLNs relative to what was achieved with oral
dosing of free MPA alone. Furthermore, Glyph-MPA was significantly
more potent than free MPA in inhibiting T cell proliferation in
mice challenged with antigen. Plasma MPA levels achieved were
similar following Glyph-MPA and free MPA dosing, indicating low
potential for the emergence of new systemic side effects.
Additionally, a prodrug of a fluorescent tracer was shown to
rapidly accumulate in MLNs following administration. Together,
these findings provide further support of the potential of the
Glyph technology to enable oral administration of small molecule
drugs directly to the lymphatic system, including drugs with
immunomodulatory properties.
“What’s interesting here is the idea that one might be able to
target and administer immunomodulatory drugs to the mesenteric
lymph nodes and therefore selectively suppress immune responses
that emanate from those lymph nodes,” said Joseph Bolen, Ph.D.,
Chief Scientific Officer at PureTech. “The Glyph platform is a
highly innovative technology and we are moving quickly to build off
this foundational research and establish additional therapeutic
applications, including bypassing first pass metabolism and
enabling oral bioavailability of parenteral drugs.”
About the GlyphTM Platform Glyph is PureTech’s synthetic
lymphatic-targeting chemistry platform, which is designed to employ
the body’s natural lipid absorption and transport process to orally
administer drugs via the lymphatic system. PureTech believes this
technology has the potential to (1) enable direct modulation of the
immune system via drug targets present in mesenteric lymph nodes
and (2) provide a broadly applicable means of enhancing the
bioavailability of orally-administered drugs that would otherwise
become inactive by first-pass liver metabolism. PureTech has
demonstrated proof-of-concept by achieving therapeutically relevant
plasma levels following oral administration of a neurosteroid,
allopregnanolone, in small animal and non-human primate model
systems. This and other work have resulted in the generation of
PureTech’s lead Glyph product candidate, LYT-300 (oral
allopregnanolone), which is expected to enter a clinical trial by
the end of 2021. Additionally, PureTech announced an alliance with
Boehringer Ingelheim in 2019, which is initially focused on
evaluating the feasibility of applying the Glyph technology
platform to one of its immuno-oncology product candidates. PureTech
retains rights to all other applications of this technology outside
of the specific BI candidates being studied. The Glyph technology
platform is based on the pioneering research of Christopher Porter,
Ph.D., and his team at the Monash Institute of Pharmaceutical
Sciences at Monash University in Melbourne, which PureTech has
exclusively licensed.
About PureTech Health PureTech is a clinical-stage
biotherapeutics company dedicated to discovering, developing and
commercializing highly differentiated medicines for devastating
diseases, including intractable cancers, lymphatic and
gastrointestinal diseases, central nervous system disorders and
inflammatory and immunological diseases, among others. The Company
has created a broad and deep pipeline through the expertise of its
experienced research and development team and its extensive network
of scientists, clinicians and industry leaders. This pipeline,
which is being advanced both internally and through PureTech’s
Founded Entities, as of the date of PureTech’s most recently filed
Registration Statement on Form 20-F, was comprised of 24 products
and product candidates, including two that have received FDA
clearance and European marketing authorization. All of the
underlying programs and platforms that resulted in this pipeline of
product candidates were initially identified or discovered and then
advanced by the PureTech team through key validation points based
on the Company’s unique insights into the biology of the brain,
immune and gut, or BIG, systems and the interface between those
systems, referred to as the BIG Axis.
For more information, visit www.puretechhealth.com or connect
with us on Twitter @puretechh.
Cautionary Note Regarding Forward-Looking Statements This
press release contains statements that are or may be
forward-looking statements, including statements that relate to the
company's future prospects, developments, and strategies. The
forward-looking statements are based on current expectations and
are subject to known and unknown risks and uncertainties that could
cause actual results, performance and achievements to differ
materially from current expectations, including, but not limited
to, our expectations regarding the potential therapeutic benefits
of our product candidates, our expectations regarding the GlyphTM
platform and those risks and uncertainties described in the risk
factors included in PureTech Health plc’s registration statement on
Form 20-F, declared effective by the Securities and Exchange
Commission on November 12, 2020 and other regulatory filings for
PureTech Health plc. These forward-looking statements are based on
assumptions regarding the present and future business strategies of
the company and the environment in which it will operate in the
future. Each forward-looking statement speaks only as at the date
of this press release. Except as required by law and regulatory
requirements, neither the company nor any other party intends to
update or revise these forward-looking statements, whether as a
result of new information, future events or otherwise.
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version on businesswire.com: https://www.businesswire.com/news/home/20210225005700/en/
Investors Allison Mead Talbot +1 617 651 3156
amt@puretechhealth.com
U.S. media Stephanie Simon +1 617 581 9333
stephanie@tenbridgecommunications.com
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