RCS - PureTech Health PLC - PRTC's Seaport Advances 2nd Candidate Into Clinic

Puretech HealthAnnouncement

11/09/2025 12:15

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RNS Number : 9396Y  PureTech Health PLC  11 September 2025

11 September 2025

PureTech Health plc

 

PureTech Founded Entity Seaport Therapeutics Advances Second Therapeutic
Candidate into Clinical Development with Dosing of First Participant in Phase
1 Study of GlyphAgo(TM) (SPT-320) in Healthy Volunteers

 

GlyphAgo is an oral prodrug of agomelatine, a medicine with established
clinical efficacy in

generalized anxiety disorder (GAD)

 

GlyphAgo is designed to overcome a key limitation of agomelatine by shifting
absorption toward the intestinal lymphatics, avoiding first-pass liver
metabolism, and increasing systemic exposure of the drug

 

Phase 1 proof-of-concept study will evaluate the safety, tolerability, and
pharmacokinetics of GlyphAgo and is designed to demonstrate therapeutic levels
of agomelatine at lower doses that reduce liver exposure

 

PureTech Health plc (https://puretechhealth.com/) (Nasdaq: PRTC, LSE: PRTC)
("PureTech" or the "Company"), a hub-and-spoke biotherapeutics company
dedicated to giving life to science and transforming innovation into value,
noted that its Founded Entity, Seaport Therapeutics (http://www.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 participant has been dosed in the Phase 1 study of
GlyphAgo™ (SPT-320 or Glyph Agomelatine).

 

GlyphAgo is being developed to treat generalized anxiety disorder (GAD), one
of the most common mental health conditions worldwide. It is a "Glyphed" oral
prodrug of agomelatine, a medicine that has already shown clinical benefit in
multiple third-party studies of GAD, but whose use has been limited by
liver-related side effects. Using Seaport's proprietary Glyph™ platform,
GlyphAgo is designed to improve how the drug is absorbed in the body so that
people living with GAD may potentially achieve a therapeutic benefit at lower
doses with reduced liver exposure.

 

The study marks the second therapeutic candidate from Seaport's pipeline to
advance into clinical-stage development.

 

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

 

Seaport Therapeutics Advances Second Therapeutic Candidate into Clinical
Development with Dosing of First Participant in Phase 1 Study of GlyphAgo(TM)
(SPT-320) in Healthy Volunteers

 

GlyphAgo is an oral prodrug of agomelatine, a medicine with established
clinical efficacy in four out of four previous third-party randomized,
placebo-controlled studies in

generalized anxiety disorder (GAD)

 

Building on agomelatine's proven clinical efficacy, GlyphAgo is designed to
overcome a key limitation of agomelatine by shifting absorption toward the
intestinal lymphatics, avoiding first-pass liver metabolism, and increasing
systemic exposure of the drug

 

Phase 1 proof-of-concept study will evaluate the safety, tolerability, and
pharmacokinetics of GlyphAgo and is designed to demonstrate therapeutic levels
of agomelatine at lower doses that reduce liver exposure

 

Boston, MA - September 11, 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 participant
has been dosed in the Phase 1 study of GlyphAgo™ (SPT-320 or Glyph
Agomelatine), a "Glyphed" oral prodrug of agomelatine in development for the
treatment of generalized anxiety disorder (GAD). The study will evaluate the
safety, tolerability, and pharmacokinetics of GlyphAgo in healthy adult
volunteers. This marks the second therapeutic candidate in Seaport's pipeline
in clinical development.

 

Agomelatine, a clinically validated melatonin receptor agonist and serotonin
2C receptor antagonist, is an effective anxiolytic and antidepressant approved
for the treatment of GAD in Australia and major depressive disorder (MDD) in
Australia and the European Union (EU). In GAD, agomelatine has demonstrated
statistically significant separation from placebo in four out of four
third-party placebo-controlled studies and has better efficacy and
tolerability - including reduced risk of abuse potential, sexual dysfunction,
and weight gain - than standard of care drugs, like selective serotonin
reuptake inhibitors (SSRIs) or benzodiazepines. However, over 90 percent of
unmodified agomelatine is lost to first-pass liver metabolism and its use has
been limited by dose-dependent liver enzyme elevations and the need for
frequent liver monitoring.

 

Using Seaport's proprietary Glyph™ platform, GlyphAgo is designed to
overcome this limitation by shifting absorption toward the intestinal
lymphatics, avoiding first-pass liver metabolism, and increasing systemic
exposure of agomelatine. As a result, GlyphAgo has the potential to achieve
exposure levels that have demonstrated efficacy in GAD at a lower dose that
does not cause an increase in liver enzymes and reduces or eliminates the need
for liver function testing.

 

"Anxiety disorders are the most prevalent neuropsychiatric disorders,
impacting nearly 30 percent of adults at some point in their lives, with GAD
alone affecting approximately 100 million adults worldwide. Despite this, in
the U.S., no new drugs or mechanisms have been approved for GAD in decades,"
said Antony Loebel, M.D., Chief Medical Officer, President of Clinical
Development at Seaport Therapeutics. "Our Phase 1 proof-of-concept study could
be highly derisking for the GlyphAgo program, as agomelatine's efficacy in GAD
is already well established. The key question is whether we can achieve
effective exposure at a lower dose, which would demonstrate GlyphAgo's ability
to avoid agomelatine's dose-dependent liver issues. We believe GlyphAgo has
the potential to redefine the treatment landscape for GAD and represents an
important clinical advancement for patients."

 

The Phase 1 study will be conducted in multiple parts to evaluate the safety,
tolerability, and pharmacokinetics of GlyphAgo compared to agomelatine. It
will include single- and multiple-ascending dose phases, as well as a
food-effect crossover portion, using both open-label and placebo-controlled
designs.

 

In a series of preclinical proof-of-concept studies, GlyphAgo was shown to
enhance lymphatic absorption and provide significantly higher systemic
exposures of agomelatine compared to agomelatine alone. Specifically, oral
dosing of GlyphAgo resulted in over 50 percent of agomelatine being
transported through the mesenteric lymphatics versus less than one percent for
orally dosed agomelatine alone. The data
(https://seaporttx.com/press-release/seaport-therapeutics-presents-new-preclinical-data-on-spt-320-glyph-agomelatine-at-the-society-of-biological-psychiatry-sobp-annual-meeting/)
, which were presented at the Society of Biological Psychiatry (SOBP) Annual
Meeting 2025, also showed that oral dosing of GlyphAgo increased plasma
exposure of agomelatine by over 10-fold versus agomelatine alone.

 

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 GlyphAgo(TM) (SPT-320 or Glyph Agomelatine)

GlyphAgo (SPT-320 or Glyph Agomelatine), an oral prodrug of agomelatine, is in
clinical stage development with the potential to be the first new treatment
for generalized anxiety disorder (GAD) in decades. Using the
Glyph(TM) platform, GlyphAgo was designed to bypass first-pass liver
metabolism in order to lower the dose, reduce liver exposure, and reduce or
eliminate the need for liver enzyme monitoring. Agomelatine is a clinically
validated anxiolytic and antidepressant approved for GAD in Australia and
major depressive disorder (MDD) in Australia and the European Union (EU). The
use of agomelatine has been limited by high first-pass liver metabolism
resulting in liver enzyme elevations in some patients and frequent, burdensome
liver enzyme monitoring requirements. GlyphAgo is currently in a Phase 1
proof-of-concept study to evaluate the safety, tolerability, and
pharmacokinetics in healthy adult volunteers.

 

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 Health is a hub-and-spoke biotherapeutics company dedicated to giving
life to science and transforming innovation into value. We do this through a
proven, capital-efficient R&D model focused on opportunities with
validated pharmacology and untapped potential to address significant patient
needs. This strategy has produced dozens of therapeutic candidates, including
three that have received U.S. FDA approval. By identifying, shaping, and
de-risking these high-conviction assets, and scaling them through dedicated
structures backed by external capital, we accelerate their path to patients
while creating sustainable value for shareholders.

 

For more information, visit 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 GlyphAgo™ and the Glyph platform, the design and expected
safety and efficacy outcomes of the Phase 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
 FTI Consulting
 Ben Atwell, Rob Winder
 +44 (0) 20 3727 1000
 puretech@fticonsulting.com (mailto:puretech@fticonsulting.com)
 US Media
 Ten Bridge Communications
 Justin Chen
 +1 609 578 7230
 jchen@tenbridgecommunications.com

 

Sources:

Ansara E. D. (2020). Management of treatment-resistant generalized anxiety
disorder. Mental Health Clinician, 10(6), 326-334. Mental disorders; World
Health Organization, 2022

 

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