RCS - PureTech Health PLC - PRTC’s Seaport Begins Phase 2b Study in MDD

Puretech HealthAnnouncement

17/07/2025 12:15

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RNS Number : 5104R  PureTech Health PLC  17 July 2025

17 July 2025

PureTech Health plc

 

PureTech Founded Entity Seaport Therapeutics Announces First Patient Dosed in
Phase 2b BUOY-1 Study of GlyphAllo(TM) (SPT-300) in Major Depressive Disorder
(MDD), With or Without Anxious Distress

 

BUOY-1 builds on successful Phase 1 and Phase 2a data with GlyphAllo - a novel
oral prodrug of allopregnanolone and a potential first-in-class treatment for
MDD

 

Allopregnanolone has demonstrated rapid antidepressant and anxiolytic activity
in clinical settings, but its clinical scope was previously constrained by
limitations that Glyph™ is specifically designed to solve

 

PureTech Health plc (https://puretechhealth.com/) (Nasdaq: PRTC, LSE: PRTC)
("PureTech"), a clinical-stage biotherapeutics company, noted that its
Founded Entity, Seaport Therapeutics (https://seaporttx.com/) , ("Seaport") a
clinical-stage biopharmaceutical company that is advancing novel
neuropsychiatric medicines with a proven strategy and team, today announced
that the first patient has been dosed in the Phase 2b BUOY-1 study of
GlyphAllo(TM) (SPT-300 or Glyph Allopregnanolone) in major depressive disorder
(MDD) with or without anxious distress.

 

GlyphAllo is a novel, "Glyphed" oral prodrug of allopregnanolone, an
endogenous molecule that has been shown to dampen stress. Allopregnanolone has
been clinically validated in third-party trials as a rapidly acting
antidepressant with anxiolytic effects, but its scope of clinical use was
previously constrained by limitations that the Glyph(TM) platform is
specifically designed to solve. GlyphAllo has the potential to be a
first-in-class treatment for patients with MDD, including those with or
without anxious distress.

 

The full text of the announcement from Seaport is as follows:

 

Seaport Therapeutics Announces First Patient Dosed in Phase 2b BUOY-1 Study of
GlyphAllo(TM) (SPT-300) in Major Depressive Disorder (MDD), With or Without
Anxious Distress

 

BUOY-1 builds on successful Phase 1 and Phase 2a data with GlyphAllo - a novel
oral prodrug of allopregnanolone and a potential first-in-class treatment for
MDD

 

Allopregnanolone has demonstrated rapid antidepressant and anxiolytic activity
in clinical settings, but its clinical scope was previously constrained by
limitations that Glyph™ is specifically designed to solve

 

Boston, MA - July 17, 2025 - Seaport Therapeutics (http://www.seaporttx.com)
("Seaport" or the "Company"), a clinical-stage biopharmaceutical company that
is advancing novel neuropsychiatric medicines with a proven strategy and team,
today announced that the first patient has been dosed in the Phase 2b BUOY-1
study of GlyphAllo(TM) (SPT-300 or Glyph Allopregnanolone) in major depressive
disorder (MDD) with or without anxious distress. GlyphAllo is a novel,
"Glyphed" oral prodrug of allopregnanolone, an endogenous molecule that has
been shown to dampen stress. Allopregnanolone has been clinically validated in
third-party trials as a rapidly acting antidepressant with anxiolytic effects,
but its scope of clinical use was previously constrained by limitations that
the Glyph(TM) platform is specifically designed to solve. GlyphAllo has the
potential to be a first-in-class treatment for patients with MDD, including
those with or without anxious distress.

 

"The initiation of BUOY-1 marks a significant milestone for Seaport's
pipeline, bringing us closer to a potential new treatment for major
depression, which impacts around 280 million people globally - nearly 60
percent of whom also experience anxious distress," said Daphne Zohar,
Co-Founder and Chief Executive Officer at Seaport Therapeutics. "This is an
important step on our journey to deliver new treatments for patients living
with depression, anxiety, and other neuropsychiatric conditions."

 

BUOY-1 is a global, randomized, double-blind, placebo-controlled study that
will evaluate the efficacy, safety, and tolerability of GlyphAllo in adults
with MDD, with or without anxious distress, a subtype of depression
characterized by significant anxiety. The study is expected to enroll up to
approximately 360 patients, randomized 1:1 to receive either GlyphAllo or
placebo once-daily over a six-week treatment period. The primary endpoint of
the study is the change from baseline at six weeks in the Hamilton Depression
Rating Scale-17 (HAM-D-17), a gold-standard depression severity rating scale.
Following the initial treatment period, eligible patients may enter an
open-label extension phase, during which all participants will receive
GlyphAllo for up to an additional six weeks.

 

"CNS clinical trials are inherently complex, and we are applying our team's
extensive expertise to implement a high-quality study," said Antony Loebel,
M.D., Chief Medical Officer, President of Clinical Development at Seaport
Therapeutics. "We are confident that our rigorous clinical trial execution,
including an emphasis on the quality of patient enrollment, will build on a
proven mechanism and established clinical efficacy, to increase our likelihood
of success in developing an effective treatment for patients with depression."

 

The BUOY-1 study builds on a foundation of positive clinical data from Phase 1
and Phase 2a studies of GlyphAllo in healthy volunteers. In Phase 1, GlyphAllo
demonstrated approximately nine times greater allopregnanolone exposure than
that previously reported following oral dosing of allopregnanolone and reached
similar exposures to the efficacious doses of IV-infused allopregnanolone. The
two key measures used to determine allopregnanolone-associated brain activity,
EEG beta frequency power and reduction in saccadic eye velocity, confirmed
that GlyphAllo engaged with its target in a dose-dependent manner. The overall
safety data, pharmacokinetics, and pharmacodynamic findings, along with
non-clinical studies, support six-week dosing of GlyphAllo in BUOY-1.

 

In a Phase 2a proof-of-concept study in healthy volunteers using the Trier
Social Stress Test (TSST), a validated clinical model of anxiety, GlyphAllo
significantly reduced the stress hormone salivary cortisol at all post-TSST
timepoints compared to placebo, meeting the primary endpoint with a p-value of
0.0001 and demonstrating that GlyphAllo regulates
hypothalamic-pituitary-adrenal axis reactivity to acute stress. GlyphAllo was
generally well-tolerated, with adverse events that were mostly mild and
transient.

 

About the Glyph(TM) Platform

Glyph is Seaport's proprietary technology platform which uses the lymphatic
system to enable and enhance the oral administration of drugs. With the Glyph
platform, drugs are absorbed like dietary fats through the intestinal
lymphatic system and transported into circulation. The Glyph platform has the
potential to be widely applied to many therapeutic molecules that have high
first-pass metabolism otherwise leading to low bioavailability and/or side
effects, including liver enzyme elevations or hepatotoxicity. For each
program, Seaport leverages its Glyph platform to create unique sets of
prodrugs with differentiated profiles, including lymphatic transport and
conversion characteristics, as potential candidates to advance into
preclinical and clinical proof-of-concept studies. Seaport exclusively
licensed this technology from Monash University based on the pioneering
research of the Porter Research Group. Advanced initially at PureTech Health
and now at Seaport, Glyph has been applied to create therapeutic candidates
for the Company's pipeline resulting in new intellectual property, including
composition of matter. The group and its collaborators have published research
in Nature Metabolism (https://www.nature.com/articles/s42255-021-00457-w)
, Frontiers in Pharmacology (https://doi.org/10.3389/fphar.2022.879660)
, Journal of Controlled Release
(https://www.sciencedirect.com/science/article/pii/S0168365921000717?via%3Dihub)
 and Molecular Pharmaceutics
(https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.4c01272)  supporting the
Glyph platform's capabilities. See Glyph in action here
(https://seaporttx.com/our-pipeline/#glyph_in_action) .

 

About GlyphAllo(TM) (SPT-300 or Glyph Allopregnanolone)

GlyphAllo (SPT-300 or Glyph Allopregnanolone), an oral prodrug of
allopregnanolone, is in clinical stage development for the treatment of major
depressive disorder (MDD) with or without anxious distress. Allopregnanolone,
an endogenous molecule that has been shown to dampen stress, has
antidepressant and anxiolytic activity and sleep-promoting effects but poor
oral bioavailability due to substantial first-pass hepatic metabolism.
Allopregnanolone was previously only approved as an intravenous infusion,
which limited the scope of its clinical use. A synthetic analog of
allopregnanolone was previously evaluated in MDD and showed promise but may
not retain the activity, potency and the breadth of the natural biological
response of endogenous allopregnanolone. In a Phase 1 clinical study,
GlyphAllo demonstrated oral bioavailability, tolerability and
γ-aminobutyric-acid type A (GABA(A)) receptor target engagement in healthy
volunteers. In a Phase 2a clinical study, GlyphAllo demonstrated initial
proof-of-concept in the Trier Social Stress Test, a validated clinical model
of anxiety in healthy volunteers. GlyphAllo is currently being evaluated in
the Phase 2b BUOY-1 study for MDD, with or without anxious distress.

 

About Seaport Therapeutics

Seaport Therapeutics is a clinical-stage biopharmaceutical company advancing
the development of novel neuropsychiatric medicines in areas of high unmet
patient needs. The Company has a proven strategy of advancing clinically
validated mechanisms previously held back by limitations that are overcome
with its proprietary Glyph technology platform. All the therapeutic
candidates in its pipeline of first and best-in-class medicines are based on
the Glyph platform, which is uniquely designed to enable oral bioavailability,
bypass first-pass metabolism and reduce liver enzyme elevations or
hepatotoxicity and other side effects. Seaport is led by an experienced team
that invented and advanced important neuropsychiatric medicines and is guided
by an extensive network of renowned scientists, clinicians, and key opinion
leaders. For more information, please visit www.seaporttx.com
(http://www.seaporttx.com) .

 

About PureTech Health

PureTech is a clinical-stage biotherapeutics company dedicated to giving life
to new classes of medicine to change the lives of patients with devastating
diseases. The Company has created a broad and deep portfolio through its
experienced research and development team and its extensive network of
scientists, clinicians, and industry leaders that is being advanced both
internally and through its Founded Entities. PureTech's R&D engine has
resulted in the development of 29 therapeutics and therapeutic candidates,
including three that have been approved by the U.S. Food and Drug
Administration. A number of these programs are being advanced by PureTech or
its Founded Entities in various indications and stages of clinical
development, including registration-enabling studies. All of the underlying
programs and platforms that resulted in this portfolio of therapeutic
candidates were initially identified or discovered and then advanced by the
PureTech team through key validation points.

 For more information, visit www.puretechhealth.com
(http://www.puretechhealth.com) or connect with us on X (formerly 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 related to Seaport's development plans for
its pipeline of neuropsychiatric therapeutics based on the Glyph™ Platform,
the potential of GlyphAllo™ and the Glyph platform, the design and expected
safety and efficacy outcomes of the BUOY-1 study, the broader applicability of
the platform, the addressable market for Seaport's product candidates, if
approved, potential benefits to patients, and Seaport's and our future
prospects, developments 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, 2024, 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.

 

Contact:

PureTech

Public Relations

publicrelations@puretechhealth.com (mailto:publicrelations@puretechhealth.com)

Investor Relations

IR@puretechhealth.com (mailto:IR@puretechhealth.com)

 

UK/EU Media

Ben Atwell, Rob Winder

+44 (0) 20 3727 1000

puretech@fticonsulting.com (mailto:puretech@fticonsulting.com)

 

US Media

Justin Chen

+1 609 578 7230

justin@tenbridgecommunications.com (mailto:justin@tenbridgecommunications.com)

 

Sources:

Mental disorders; World Health Organization, 2022

Rosellini, A., et al (2018). Anxious distress in depressed outpatients:
Prevalence, comorbidity, and incremental validity.

 

 

 

 

 

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