TIDMPRTC
PureTech Health PLC
25 February 2021
25 February 2021
PureTech Health plc
PureTech Announces Publication of Glyph (TM) Platform
Preclinical Proof-of-Concept Study in Journal of Controlled
Release
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.
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 Glyph(TM) 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 Glyph(TM)
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.
Contact:
Investors EU media
Allison Mead Talbot Ben Atwell, Rob Winder
+1 617 651 3156 +44 (0) 20 3727 1000
amt@puretechhealth.com ben.atwell@FTIconsulting.com
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