Bioavailability of buprenorphine up to 20-fold
higher in preclinical models using prodrug generated with the Glyph
technology, driven by transport of prodrug through the gut-draining
lymphatics
The research published in Frontiers in
Pharmacology further demonstrates the ability of the Glyph
technology to improve bioavailability and lymphatic targeting of a
range of clinically validated drugs, including buprenorphine
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 preclinical proof-of-concept demonstrating that PureTech’s Glyph
platform can enhance the oral bioavailability of buprenorphine
(BUP), a clinically-validated opioid replacement therapy, further
expanding the range of clinically-validated drug classes shown to
be amenable to the Glyph technology. The paper, published in
Frontiers in Pharmacology1, applies the Glyph technology to BUP, a
potent analgesic that is widely used for severe pain management and
opioid replacement therapy but is not currently available in an
ingestible oral dosage form due to poor oral bioavailability. In
preclinical models, the researchers observed increases in
bioavailability of up to 20-fold and statistically significant
increases in lymphatic transport.
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PureTech announced the publication of
preclinical proof-of-concept showing up to 20-fold oral
bioavailability enhancement by the Glyph platform of buprenorphine,
a clinically-validated opioid replacement therapy. The paper was
published by PureTech collaborator, Christopher Porter, Ph.D.,
Director of the Monash Institute of Pharmaceutical Sciences at
Monash University in Melbourne, in the journal Frontiers in
Pharmacology. (Photo: Business Wire)
“The therapeutic potential of buprenorphine is potentially
limited by a lack of systemic exposure after the administration of
a capsule formulation that can be swallowed. The ability to develop
an oral buprenorphine product with high bioavailability could
potentially address a range of important unmet clinical needs and
offer more convenience for patients,” said Christopher Porter,
Ph.D., Director of the Monash Institute of Pharmaceutical Sciences
at Monash University in Melbourne, lead author of the study and
PureTech collaborator. “Results from this study further amplify the
breadth of the Glyph delivery technology and its ability to use new
chemistry and molecules for versatile applications.”
The Glyph technology generates novel orally dosed prodrugs by
reversibly linking small molecule drugs to dietary fat molecules.
This linkage is designed to channel the drugs directly into the
systemic circulation via the lymphatic system, thereby bypassing
first-pass liver metabolism which typically degrades many drugs and
reduces their systemic exposure. The Glyph technology is being
developed to be applicable to a range of clinically validated drugs
with poor bioavailability, including neuromodulators such as
allopregnanolone (with the clinical-stage therapeutic candidate,
LYT-300) or immune modulators that could directly target the
mesenteric lymph nodes.
“The research serves as another proof-of-concept for our Glyph
platform and how this innovative drug delivery technology can be
applied to a range of diseases,” said Joseph Bolen, Ph.D., Chief
Scientific Officer of PureTech. “This latest research reinforces
our commitment to leveraging validated biology to accelerate the
development of the Glyph portfolio to improve the oral
bioavailability and/or lymphatic targeting of proven drugs.”
PureTech’s LYT-300 is the first therapeutic candidate generated
by the Glyph technology platform to enter the clinic. LYT-300 is an
oral formulation of the clinically validated neurosteroid
allopregnanolone, in development for the potential treatment of a
range of neurological and neuropsychological conditions. An
injectable formulation of allopregnanolone is approved by the
United States Food and Drug Administration (FDA) for the treatment
of postpartum depression as a 60-hour infusion, a method of
administration that has inherent limitations. Synthetic oral
analogs of allopregnanolone have had variable clinical success, and
their comparable activity with natural allopregnanolone remains to
be established.
About the Glyph™ Technology Platform
The Glyph technology is PureTech's synthetic lymphatic-targeting
chemistry platform which is designed to employ the lymphatic
system's natural lipid absorption and transport process to enable
the oral administration of therapeutics. The Glyph technology
reversibly links small molecule drugs to dietary fat molecules,
creating a novel prodrug. The linked fat molecule re-routes the
drug's normal path to the systemic circulation, bypassing the liver
and instead moving from the gut into the lymphatic vessels that
normally process dietary fats. 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 be reduced by
first-pass liver metabolism. PureTech is leveraging validated
biology to accelerate the development of a Glyph portfolio,
prioritizing highly characterized drugs to enhance with the Glyph
technology based on the potential value unlocked in improving their
oral bioavailability or lymphatic targeting. PureTech's lead Glyph
therapeutic candidate, LYT-300 (oral allopregnanolone), is being
evaluated in a Phase 1 study, with results expected in the second
half of 2022. PureTech has exclusively licensed the Glyph
technology platform, which is based on the pioneering research of
Christopher Porter, Ph.D., and his research group at the Monash
Institute of Pharmaceutical Sciences at Monash University. The
Porter Research Group and collaborators have published research in
Frontiers in Pharmacology, Nature Metabolism and the Journal of
Controlled Release supporting the Glyph platform's ability to
directly target the lymphatic system with a variety of
therapies.
About PureTech Health
PureTech is a clinical-stage biotherapeutics company dedicated
to discovering, developing and commercializing highly
differentiated medicines for devastating diseases, including
inflammatory, fibrotic and immunological conditions, intractable
cancers, lymphatic and gastrointestinal diseases and neurological
and neuropsychological disorders, 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, is comprised of 25 therapeutics and therapeutic
candidates, including two that have received both U.S. FDA
clearance and European marketing authorization, as of the date of
PureTech's most recently filed Half Year Report and corresponding
Form 6-K. All of the underlying programs and platforms that
resulted in this pipeline of therapeutic 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 within the meaning of the Private
Securities Litigation Reform Act of 1995. All statements contained
in this press release that do not relate to matters of historical
fact should be considered forward-looking statements, including
without limitation those statements that relate to expectations
regarding the potential therapeutic benefits of our therapeutic
candidates or platform technologies, our expectations regarding the
Glyph platform and PureTech’s future prospects, development plans
and strategies. The forward-looking statements are based on current
expectations and are subject to known and unknown risks,
uncertainties and other important factors that could cause actual
results, performance and achievements to differ materially from
current expectations, including, but not limited to, those risks,
uncertainties and other important factors described under the
caption "Risk Factors" in our Annual Report on Form 20-F for the
year ended December 31, 2020 filed with the SEC and in our other
regulatory filings. 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, we disclaim any obligation to update or revise these
forward-looking statements, whether as a result of new information,
future events or otherwise.
[1] Hu, L., Quach, T., Han, S., Lim, S.F., Senyschyn, D.,
Trevaskis, N.L., Simpson, J.S., Porter, C.J.H. Self immolative
glyceride mimetic prodrugs promote lymphatic transport, avoid first
pass metabolism and enhance bioavailability. Angew. Chem. Ind. Ed.
(2016) 55, 13700-13705.
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PureTech Public Relations
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Nichole Sarkis +1 774 278 8273
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