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RNS Number : 1854Z  PureTech Health PLC  02 April 2026

2 April 2026

PureTech Health plc

 

PureTech Founded Entity Seaport Therapeutics Announces Positive Proof of
Concept Topline Results from Ongoing Phase 1 Trial of GlyphAgo(TM) in Healthy
Volunteers

 

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 positive
topline data from portions of its ongoing Phase 1 proof-of-concept clinical
trial evaluating GlyphAgo(TM) (SPT-320(TM) or Glyph Agomelatine). GlyphAgo is
a novel, Glyphed oral prodrug of agomelatine in development for generalized
anxiety disorder (GAD) and the second clinical-stage candidate from Seaport's
pipeline.

 

Based on the data shared today, Seaport announced plans to advance GlyphAgo
into two parallel trials, a Phase 2a proof-of-pharmacology trial to evaluate
the potential sleep benefit of GlyphAgo in patients with GAD and a Phase 2b
randomized placebo-controlled trial in GAD that is designed to be
registration-enabling.

 

The GlyphAgo 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 Positive Proof of Concept Topline Results from
Ongoing Phase 1 Trial of GlyphAgo(TM) in Healthy Volunteers

 

GlyphAgo achieved therapeutic exposures of agomelatine at doses projected to
avoid liver enzyme elevations and reduce or eliminate the need for liver
function testing that has previously limited agomelatine's clinical use

 

 GlyphAgo demonstrated a statistically significant 6.8-fold increase in
bioavailability compared to unmodified agomelatine in healthy volunteers,
exceeding the program's 2-fold target to mitigate liver exposure

 

GlyphAgo substantially reduced pharmacokinetic (PK) variability by 10-fold
compared to unmodified agomelatine

 

GlyphAgo was well-tolerated across all evaluated doses, and no serious or
severe adverse events or liver-related adverse effects were reported

 

BOSTON, April 2, 2026 - Seaport Therapeutics (https://seaporttx.com/)
 ("Seaport" or the "Company"), a clinical-stage therapeutics company
advancing novel neuropsychiatric medicines with a proven strategy and team,
today announced positive topline data from its single-ascending dose (SAD) and
crossover portions of its Phase 1 proof-of-concept clinical trial evaluating
GlyphAgo(TM) (SPT-320(TM) or Glyph Agomelatine), a novel, Glyphed oral prodrug
of agomelatine in development for generalized anxiety disorder (GAD). The
clinical proof-of-concept topline results demonstrated that GlyphAgo exceeded
the program's target of a 2-fold increase in bioavailability compared to
unmodified agomelatine, achieving therapeutic levels of agomelatine at
substantially lower doses that reduce liver exposure and are projected to
reduce or eliminate the need for liver function testing.

 

In the head-to-head crossover portion of the trial, GlyphAgo demonstrated a
6.8-fold increase in bioavailability of agomelatine compared to unmodified
orally administered agomelatine. GlyphAgo also showed significantly lower
(10-fold) PK variability compared to unmodified agomelatine. The crossover
portion included participants who were taking estrogen-containing oral
contraceptives that are known to increase agomelatine exposure due to liver
drug-drug interaction. In contrast, GlyphAgo exposure was unaffected by oral
contraceptives, further supporting the ability of GlyphAgo to bypass
first-pass liver metabolism. GlyphAgo demonstrated a 9.6 to 14.5-fold increase
in dose-normalized exposure compared to agomelatine in a separate SAD portion
of the trial in which no participants were on oral contraceptives. GlyphAgo
was well tolerated and no liver-related adverse events (AEs) were observed.
The completed SAD and crossover portions of the trial, which included
approximately 130 participants, conclude the PK proof-of-concept objectives of
the trial, while the ongoing multiple-ascending dose (MAD) portion of this
trial - conducted with only GlyphAgo - is intended to further characterize the
safety and PK of repeat-dosing of GlyphAgo.

 

"These topline data, from a well-powered Phase 1 trial, strengthen our
conviction in GlyphAgo's potential and provide further clinical validation for
the Glyph platform," said Daphne Zohar, Co-Founder and Chief Executive Officer
at Seaport Therapeutics. "Based on these data, we plan to advance GlyphAgo
into two parallel trials, a Phase 2a proof-of-pharmacology trial to evaluate
the potential sleep benefit of GlyphAgo in patients with GAD, and a Phase 2b
trial in GAD, that is a randomized placebo-controlled trial designed to be
registration-enabling. We believe that GlyphAgo has the potential to bring
patients with generalized anxiety disorder what could be the first new therapy
in decades in the U.S. for this underserved and debilitating disorder."

 

Agomelatine, a clinically validated MT1/MT2 melatonin receptor agonist and
serotonin 2C (5-HT2C) 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).
Agomelatine's label in both Australia and the EU requires liver function
testing before initiating treatment, during treatment, and upon increasing the
dose. Agomelatine is not approved in the U.S.

 

"In GAD, agomelatine has demonstrated robust and statistically significant
separation from placebo in four third-party placebo-controlled studies 1 
(#_ftn1) (-4) and has been observed in meta-analysis to have better efficacy
and tolerability than selective serotonin-reuptake inhibitors or
benzodiazepines," said Steven Paul, M.D., Co-Founder and Board Chair at
Seaport Therapeutics. "Despite this positive profile, over 90 percent of
unmodified agomelatine is lost to first-pass metabolism and its use has been
limited by dose-dependent liver enzyme elevations. The enhanced pharmaceutical
properties of GlyphAgo and resulting markedly reduced inter-individual
variability in systemic exposure to agomelatine support our clinical
development of GlyphAgo in GAD."

 

Using Seaport's proprietary Glyph(TM) platform, GlyphAgo is designed to
enhance lymphatic absorption and avoid first-pass liver metabolism, thereby
enhancing oral bioavailability and reducing side effects. By leveraging an
alternative absorption pathway via the intestinal lymphatic system used by
dietary fats, GlyphAgo is designed to increase systemic exposure of
agomelatine, enabling exposure levels of agomelatine that are effective in GAD
but at a lower dose that reduces liver exposure and reduces or eliminates the
need for liver function testing. Based on the data that Seaport has generated
to date, GlyphAgo has the potential to become a leading treatment for GAD.

 

"Agomelatine combines a differentiated mechanism with a favorable efficacy and
tolerability profile in GAD, but its potential has been previously limited by
first-pass liver metabolism and the need for burdensome liver testing," said
Daniel Bonner, Ph.D., Co-Founder and Senior Vice President, Platform, at
Seaport Therapeutics. "These results show that GlyphAgo exceeded the targeted
improvement in bioavailability, achieving robust exposure, and a more
consistent PK profile at a substantially lower dose of agomelatine."

 

Phase 1 Trial Design

The Phase 1 proof-of-concept trial is being conducted in multiple parts to
evaluate the safety, tolerability, and PK of GlyphAgo and to compare the PK of
GlyphAgo to agomelatine alone. The trial includes single and
multiple-ascending dose cohorts, as well as a crossover portion, (including
both food-effect and within-participant comparison between GlyphAgo and
agomelatine), using both open-label and placebo-controlled designs. In the SAD
portion of the Phase 1 trial, healthy volunteers received a single
administration of either ascending doses of GlyphAgo or a 25 mg dose of
agomelatine, an approved efficacious dose in Australia and the EU, to assess
PK parameters, including area under the curve (AUC), a measure of overall
exposure, and Cmax, or peak plasma concentrations. In the SAD portion,
participants were healthy volunteers with no evidence of liver impairment who
were not taking any medications or supplements known to alter the PK of
agomelatine, including fluvoxamine or estrogen-containing oral contraceptives.
In the crossover portion, participants were randomized to one of two sequences
designed to assess the food effect on a single dose level of GlyphAgo and
compare it with a 25 mg dose of agomelatine. Both sequences evaluated GlyphAgo
under fed and fasted conditions before agomelatine, a structure chosen to
avoid confounding GlyphAgo safety results with agomelatine's known liver
toxicity.

 

Topline Results

 

Crossover Portion

·    GlyphAgo demonstrated a 6.8-fold increase in dose-normalized AUC
compared to agomelatine (90% confidence interval, 4.7 to 10.0x; geometric
means). In this portion of the trial, exposure provided by GlyphAgo and
unmodified agomelatine were compared head-to-head within the same
participants.

·    Statistically significantly lower PK variability (10-fold lower
geometric CV% of AUC(0-24)) was observed between participants dosed with
GlyphAgo compared to agomelatine 25 mg (p< 0.0001).

·    It was observed that there is no food effect on agomelatine exposure
with GlyphAgo treatment.

·    No clinically significant changes in liver-related laboratory
parameters were observed, including alanine aminotransferase (ALT), aspartate
aminotransferase (AST), or bilirubin.

·    GlyphAgo achieved a 1.9-fold increase in dose-normalized maximum
plasma concentration (Cmax) compared to agomelatine (90% confidence interval,
1.2 to 3.0x).

·    This portion included participants (23%) taking estrogen-containing
oral contraceptives, which are known to increase exposure of agomelatine due
to liver drug-drug interaction(5). No effect of estrogen-containing oral
contraceptives on GlyphAgo was observed.

 

SAD Portion

·    GlyphAgo demonstrated a 9.6 to 14.5-fold increase in dose-normalized
AUC compared to agomelatine and a 2.3 to 3.7-fold increase in dose-normalized
Cmax across the doses studied. Participants in the SAD portion were not taking
concomitant estrogen-containing oral contraceptives.

·    Across all evaluated dose levels, GlyphAgo was well tolerated, with
no serious or severe AEs observed and no clinically significant changes in
liver-related laboratory parameters, including ALT, AST, or bilirubin.

·    All treatment groups (GlyphAgo, agomelatine, and placebo) were
well-tolerated, with no serious or severe AEs observed.

·    GlyphAgo AUC(0-24) and Cmax increased dose-dependently over the range
of doses studied, supporting PK and dose selection for subsequent studies.

 

Seaport plans to present additional analyses from the Phase 1 trial, including
the results from the MAD portion, at future upcoming scientific meetings.

 

About GlyphAgo (SPT-320 or Glyph Agomelatine)

GlyphAgo is a novel, Glyphed oral prodrug of agomelatine, a clinically
validated anxiolytic and antidepressant that is approved for the treatment of
GAD in Australia and MDD in Australia and the EU. Using Seaport's proprietary
Glyph platform, GlyphAgo is designed to avoid first-pass liver metabolism and
increase systemic exposure of agomelatine, enabling exposure levels of
agomelatine that are effective in GAD but at a lower dose that reduces liver
exposure and reduces or eliminates the need for liver function testing. Based
on internal analyses, Seaport believes a two-fold increase in the
bioavailability of agomelatine with GlyphAgo dosing will reduce or eliminate
liver enzyme elevations. Based on the data generated to date, Seaport believes
GlyphAgo has the potential to become a leading treatment for GAD.

 

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 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
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 GlyphAgo(TM) (SPT-320(TM) or Glyph
Agomelatine) and the Glyph platform, 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)

 

 1  (#_ftnref1) Stein, D.J., et al. (2008). Efficacy of agomelatine in
generalized anxiety disorder: a randomized, double-blind, placebo-controlled
study. J Clin Psychopharmacol, 28(5), 561-566;

2. Stein, D.J., et al. (2012). Agomelatine prevents relapse in generalized
anxiety disorder: a 6-month randomized, double-blind, placebo-controlled
discontinuation study. J Clin Psychiatry, 73(7), 1002-1008;

3. Stein, D.J., et al. (2014). Agomelatine in generalized anxiety disorder: an
active comparator and placebo-controlled study. J Clin Psychiatry, 75(4),
362-368;

4. Stein, D.J., et al. (2017). Efficacy and safety of agomelatine (10 or 25
mg/day) in non-depressed out-patients with generalized anxiety disorder: A
12-week, double-blind, placebo-controlled study. Eur Neuropsychopharmacol,
27(5), 526-537; 5. Slee, A., et al. (2019). Pharmacological treatments for
generalised anxiety disorder: a systematic review and network meta-analysis.
The Lancet, 393(10173), 768-777.

5
https://www.ema.europa.eu/en/documents/product-information/valdoxan-epar-product-information_en.pdf

 

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