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RNS Number : 1548Y  PureTech Health PLC  25 March 2026

25 March 2026

PureTech Health plc

 

                PureTech Founded Entity Seaport Therapeutics
Announces Publication in Science Translational Medicine Featuring
GlyphAllo(TM) (SPT-300) as the First Triglyceride-Mimetic Prodrug to Achieve
Therapeutically Relevant Drug Levels in Humans

 

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,
notes that its Founded Entity, Seaport Therapeutics, today announced the
publication of first-in-human clinical and preclinical data for GlyphAllo™
(SPT-300 or Glyph Allopregnanolone) in Science Translational Medicine.

 

The GlyphAllo program and the underlying Glyph platform were initially
advanced at PureTech, applying the Company's strategy of identifying
clinically validated pharmacology and overcoming key limitations through
targeted innovation. The Glyph platform and related programs are now being
advanced by PureTech's Founded Entity, Seaport Therapeutics.

 

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

 

Seaport Therapeutics Announces Science Translational Medicine Peer-Reviewed
Publication Featuring GlyphAllo(TM) (SPT-300) as the First
Triglyceride-Mimetic Prodrug to Achieve Therapeutically Relevant Drug Levels
in Humans

 

Newly published findings further support clinical validation of Seaport's
proprietary Glyph™ platform to enable oral dosing

 

Data supported advancement of ongoing Phase 2b clinical trial of GlyphAllo in
major depressive disorder (MDD)

 

BOSTON, March 25, 2026 - Seaport Therapeutics (https://seaporttx.com/)
 ("Seaport" or the "Company"), a clinical-stage therapeutics company focused
on inventing and developing new medicines for patients with depression,
anxiety, and other debilitating neuropsychiatric disorders with a proven
strategy and team, today announced the first comprehensive disclosure of
first-in-human clinical and preclinical data for GlyphAllo™ (SPT-300 or
Glyph Allopregnanolone), a novel, Glyphed oral prodrug of allopregnanolone,
published in Science Translational Medicine, tracing the program's pathway
from discovery through initial proof-of-concept. The peer-reviewed article,
titled "An oral allopregnanolone prodrug bypasses liver metabolism via
lymphatic transport enabling bioavailability in animals and humans," details
the design, optimization, and clinical translation of GlyphAllo, and further
supports clinical validation of Seaport's proprietary Glyph™ platform.

 

"Allopregnanolone is an endogenous molecule with a rapid onset of action and
well established, clinically validated antidepressant, anxiolytic, and
sleep-promoting effects, as demonstrated in third-party clinical trials for
the treatment of postpartum depression, a form of depression that shares
symptomatology with MDD," said Steven Paul, M.D., Co-Founder and Board Chair
at Seaport Therapeutics, and author on the paper. "GlyphAllo is our lead
investigational product candidate designed to overcome the bioavailability
limitations of allopregnanolone and deliver rapid and durable clinical
effects. With the now optimized pharmaceutical properties of GlyphAllo, we can
now study an oral prodrug of allopregnanolone as a potential new treatment for
MDD."

 

The newly published research details the discovery process driving the
creation of GlyphAllo, in which simple triglyceride-mimetic (TG-mimetic)
allopregnanolone prodrug candidates with direct conjugation of a desired drug
with lipophilic moieties were synthesized, screened, and evaluated across
preclinical models. Multiple prodrug candidates demonstrated robust lymphatic
transport and plasma release profiles consistent with achieving
therapeutically relevant allopregnanolone exposure after oral dosing. The data
further demonstrated that Glyph enabled and enhanced the oral administration
of molecules historically limited by high first-pass metabolism. The paper
describes how Seaport used the Glyph platform to optimize GlyphAllo,
demonstrating enhanced oral bioavailability in preclinical models, with oral
dosing resulting in robust lymphatic transport and systemic exposure. These
data supported the selection and advancement of GlyphAllo into Phase 1 and
Phase 2a clinical development.

 

Translation of these findings into humans was confirmed in Phase 1/2a clinical
development, which demonstrated dose-dependent, therapeutically relevant
allopregnanolone levels and pharmacodynamic effects in healthy volunteers. In
Phase 1, GlyphAllo was generally well-tolerated following single- and
multiple-ascending oral doses ranging from 70-1000 mg and provided
therapeutically relevant plasma exposures of allopregnanolone. In the Phase 2a
initial proof-of-concept trial using the Trier Social Stress Test (TSST), a
validated clinical model of anxiety, a single 375 mg dose of GlyphAllo
significantly reduced levels of salivary cortisol versus placebo (p=0.0001),
demonstrating that GlyphAllo potently blunted the acute physiological stress
response.

 

"This pioneering work, published in Science Translational Medicine, a premier,
high-impact journal, positions GlyphAllo as a compelling drug candidate and
supports further investigation of its potential to address MDD, including in
patients with or without anxious distress," said Michael Chen, Ph.D.,
Co-Founder and Chief Scientific Officer at Seaport Therapeutics, and senior
author of the paper. "Importantly, these findings also further support the
broad compatibility of the Glyph platform to transform promising small
molecules with pharmacokinetic limitations into prodrugs with the right
properties."

 

Collectively, the results support the continued development of GlyphAllo as a
potential differentiated therapy for MDD. In July 2025, Seaport initiated
BUOY-1, a global, randomized, double-blind, placebo-controlled Phase 2b trial
evaluating the efficacy, safety, and tolerability of GlyphAllo in adults with
MDD, with or without anxious distress. Beyond GlyphAllo, the publication
highlights the broad translatability of the Glyph platform, demonstrating an
efficient, repeatable approach to creating and validating Glyph molecules that
can overcome pharmacokinetic barriers, with potential applications extending
beyond neuropsychiatry into oncology, immunology and inflammation, metabolic
disease, and obesity.

 

In addition to Dr. Paul and Dr. Chen, the research was led by Seaport authors
Jamie Simpson, Ph.D., lead author of the publication, original co-inventor of
the Glyph technology and Head of Chemistry, and Daniel Bonner, Ph.D.,
Co-Founder, Senior Vice President, Platform. The research was conducted in
collaboration with Monash University under the direction of Christopher
Porter, Ph.D., an original co-inventor of the Glyph technology and Director of
the Monash Institute of Pharmaceutical Sciences.

 

Read the paper here: www.science.org/doi/10.1126/scitranslmed.adu2352
(https://nam09.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.science.org%2Fdoi%2F10.1126%2Fscitranslmed.adu2352&data=05%7C02%7Cshannon.costello%40seaporttx.com%7Ce0a3b388caaa485a25b108de89cc6a75%7Cb9cd0f4e09304db6923caa8f427a1a09%7C0%7C0%7C639099708226088887%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=rsDaUvZ9atwpKo4U%2F1wP%2Bj13iscLMbS10gen5gUfwlc%3D&reserved=0)

 

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)
, Molecular Pharmaceutics
(https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.4c01272) , and Science
Translational Medicine
(http://www.science.org/doi/10.1126/scitranslmed.adu2352) supporting the Glyph
platform's capabilities. See Glyph in action here
(https://seaporttx.com/our-pipeline/#glyph_in_action) .

 

About Seaport Therapeutics

Seaport Therapeutics is a clinical-stage therapeutics company advancing the
development of novel neuropsychiatric medicines in areas of high unmet patient
needs. The Company's experienced team of industry leaders has a proven track
record of building successful companies that have developed and commercialized
innovative neuropsychiatric medicines.  The Company has focused its strategy
on 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 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
LinkedIn (https://www.linkedin.com/company/puretech-health/) and 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 those related to Seaport's
development plans for its pipeline of neuropsychiatric therapeutics based on
the Glyph™ Platform, the potential of GlyphAlloTM (SPT-300) and the Glyph
platform, the design and expected safety and efficacy outcomes of the Phase 2b
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
jchen@tenbridgecommunications.com (mailto:jchen@tenbridgecommunications.com)

 

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