9 May
2024
PureTech Health plc
PureTech Founded Entity
Seaport Therapeutics Presents Data from Multiple SPT-300 Trials at
Society of Biological Psychiatry (SOBP) Annual
Meeting
SPT-300 demonstrated nine
times greater allopregnanolone exposure in humans dosed orally than
published data for oral allopregnanolone,1 validating
Glyph™ platform's ability to enhance oral
bioavailability
In a Phase 2a trial,
SPT-3002 substantially reduced
stress-induced levels of cortisol, supporting Seaport's planned
studies in mood and anxiety disorders, including anxious
depression
PureTech Health plc
(Nasdaq: PRTC, LSE: PRTC) ("PureTech" or the
"Company"), a clinical-stage biotherapeutics company, noted that
its Founded Entity, Seaport
Therapeutics, a biopharmaceutical
company that is charting a proven path in neuropsychiatry, today
announced two poster presentations detailing the results from
multiple clinical trials of SPT-300 at the Society of Biological
Psychiatry Annual Meeting in Austin, TX. SPT-300 has been shown to
retain the activity and potency of natural allopregnanolone in an
oral form and has the potential to capture the breadth of the
naturally occurring neurosteroid, which is believed to have
significant therapeutic potential in a range of mood and anxiety
disorders, including anxious depression. The presentations detail
data from the first-in-human, multi-part Phase 1 trial of
SPT-300 and the Phase 2a trial of SPT-300 in the Trier Social
Stress Test, a validated clinical model of anxiety in healthy
volunteers, and include assessment of safety, tolerability,
efficacy, oral bioavailability and GABAA receptor target engagement.
The full text of the announcement
from Seaport is as follows:
Seaport Therapeutics Presents
Data from Multiple SPT-300 Trials at Society of Biological
Psychiatry (SOBP) Annual Meeting
SPT-300 demonstrated nine
times greater allopregnanolone exposure in humans dosed orally than
published data for oral allopregnanolone, validating
Glyph™ platform's ability to enhance oral
bioavailability
In a Phase 2a trial, SPT-300
substantially reduced stress-induced levels of cortisol, supporting
Seaport's planned studies in mood and anxiety disorders, including
anxious depression
BOSTON, May 9, 2024 - Seaport
Therapeutics, a clinical-stage
biopharmaceutical company that is charting a proven path in
neuropsychiatry, today announced two poster presentations detailing
the results from multiple clinical trials of SPT-300 at the Society
of Biological Psychiatry (SOBP) Annual Meeting in Austin, TX.
SPT-300 has been shown to retain the activity and potency of
natural allopregnanolone in an oral form and has the potential to
capture the breadth of the naturally occurring neurosteroid, which
is believed to have significant therapeutic potential in a range of
mood and anxiety disorders, including anxious depression. The
presentations detail data from the
first-in-human, multi-part Phase 1
trial of SPT-300 and the Phase 2a trial of
SPT-300 in the Trier Social Stress Test (TSST), a validated
clinical model of anxiety in healthy volunteers, and include
assessment of safety, tolerability, efficacy, oral bioavailability
and GABAA receptor target
engagement.
"These data summarize some of the
evidence supporting the core mechanisms of SPT-300 as we advance to
later-stage clinical studies. Our proprietary GlyphTM
platform allows SPT-300 to be absorbed like a dietary fat through
the intestinal lymphatic system and transported into circulation.
We believe this will address allopregnanolone's naturally low
bioavailability but retain its endogenous mechanism and range of
potential therapeutic effects," said Michael Chen, Ph.D.,
Co-founder and Chief Scientific Officer of Seaport Therapeutics.
"These data validate that SPT-300 has the potential to make a
difference for patients suffering from depression, anxiety and
other neuropsychiatric conditions and also provides further
validation for our Glyph platform as an elegant solution to
multiple key obstacles in neuropsychiatric drug
development."
Details of the poster presentations at SOBP
Title: A
First-in-Human Phase 1 Study of SPT-300, A First-in-Class Orally
Bioavailable Prodrug of the Neurosteroid Allopregnanolone that is
Absorbed via the Lymphatic System
Presenter: Michael C. Chen,
Ph.D.
The topline results from the
completed, multi-part Phase 1 trial of SPT-300 were reported in
December 2022. Overall, the Phase 1 trial was well tolerated and
evaluated oral bioavailability, safety, tolerability,
pharmacokinetics and GABAA target engagement. This study
included double-blind single ascending dose, multiple ascending
dose and open-label food effect parts.
Allopregnanolone is an endogenous
neurosteroid of GABAA positive allosteric modulator with
validated anti-depressant and anxiolytic activity, but orally
administered allopregnanolone is poorly bioavailable. SPT-300 is
absorbed through the intestinal lymphatic system, allowing it to
avoid first-pass metabolism. Out of 99 participants enrolled
in the first-in-human study, allopregnanolone exposure from SPT-300
was approximately nine times greater than published data for oral
allopregnanolone. SPT-300 was generally well-tolerated and resulted
in pharmacodynamic effects consistent with GABAA positive allosteric modulation. The
pharmacodynamic and pharmacokinetic properties demonstrated warrant
further clinical development. No treatment-related severe or
serious adverse events (AE) were reported, and the most common AE
was somnolence, which was mild in all cases.
Title: SPT-300, an Oral Prodrug of Allopregnanolone, Potentially
Reduces Salivary Cortisol Response to the Trier Social Stress Test
in a Randomized, Placebo-Controlled Trial in Healthy
Participants
Presenter: Michael C. Chen,
Ph.D.
The topline results from Seaport's
SPT-300 Phase 2a proof-of-concept trial were reported in November
2023. The potential of SPT-300 to reduce
physiological stress was tested in a randomized, placebo-controlled
study using the TSST, a validated clinical model of anxiety in
healthy volunteers exposed to unpredictable, novel, anticipatory
and social stress.
Among the enrolled healthy
volunteers, SPT-300 substantially reduced salivary cortisol at all
post-TSST timepoints compared to placebo and SPT-300 treated
participants had significantly reduced cortisol versus placebo from
baseline to peak (p=0.0001), meeting the study's primary endpoint and demonstrating that
SPT-300 regulates hypothalamic-pituitary-adrenal axis reactivity to
acute stress. The most common treatment-emergent adverse event was
somnolence (29% SPT-300 vs. 13% placebo), which was transient and
mild or moderate. SPT-300 was generally well-tolerated and
demonstrated GABA modulatory pharmacological activity that merits
further investigation in stress-related mood and anxiety disorders,
including anxious depression.
About SPT-300
SPT-300 (Glyph-allopregnanolone), an
oral prodrug of allopregnanolone, an endogenous neurosteroid, is in
clinical stage development for the treatment of mood and anxiety
disorders, including anxious depression. Allopregnanolone has
demonstrated therapeutic benefit in a range of neuropsychiatric
conditions, but it is only approved as an intravenous infusion,
which has limited the scope of its clinical use. Using the Glyph
platform, SPT-300 retains the activity and potency of endogenous
allopregnanolone in an oral form and has the potential to capture
the breadth of the natural biological response. In a Phase 2a
clinical trial, SPT-300 demonstrated proof-of-concept in a
validated clinical model of anxiety in healthy volunteers. SPT-300
also demonstrated oral bioavailability, tolerability and
γ-aminobutyric-acid type A (GABAA) receptor target
engagement in healthy volunteers in a Phase 1 clinical
trial.
About the Glyphä 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.
Seaport believes the Glyph technology has
the potential to be widely applied to many therapeutic molecules
that have high first-pass metabolism leading to low bioavailability
and/or side effects, including hepatotoxicity. The Glyph platform
has been refined at Seaport to efficiently generate multiple
therapeutic candidates within the company's pipeline. Seaport has
exclusively licensed this technology from Monash University
based on the pioneering research of the Porter research
group, along with the co-inventors from PureTech Health and
Seaport. The group and its collaborators have published research
in Nature
Metabolism, Frontiers in
Pharmacology and the
Journal of Controlled Release supporting the Glyph platform's capabilities.
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 GlyphTM 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
hepatotoxicity and other side effects. Seaport is led by an experienced team that was involved in
inventing and advancing KarXT and other neuropsychiatric medicines
and are guided by an extensive network of renowned scientists,
clinicians and key opinion leaders across neurological specialties.
For more information, please visit 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 pipeline 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 two that have
received both U.S. FDA clearance and European marketing
authorization and a third (KarXT) that has been filed for FDA
approval. 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
pipeline 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 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 the
therapeutic potential of SPT-300, our expectations regarding the
Glyph platform including the potential for new treatment
applications, Seaport's development plans 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, 2023, 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
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revise these forward-looking statements, whether as a result of new
information, future events or otherwise.
1U.S. Food and Drug Administration. (2018). FDA drug approval
package: Zulresso (Application No. 211,371)
2SPT-300, formerly known as LYT-300
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