Orally administered LYT-300 achieved a
statistically significant (p=0.0001) reduction in the stress
hormone response, as measured by salivary cortisol, compared to
placebo
This proof-of-concept trial demonstrating a
reduction in the physiological stress response supports the further
development of LYT-300 as a potential treatment for a range of
anxiety disorders
Anxiety disorders affect nearly 30 percent of
U.S. adults1, yet current standard-of-care treatments can have
drawbacks including mixed efficacy, abuse potential, delayed onset
of action and/or poor tolerability; LYT-300 has potential to
overcome these challenges as a novel therapeutic in an area of
serious patient need
LYT-300 was well-tolerated across the trial
with only transient mild or moderate adverse events
PureTech Health plc (Nasdaq: PRTC, LSE: PRTC) ("PureTech" or the
"Company"), a clinical-stage biotherapeutics company dedicated to
changing the lives of patients with devastating diseases, today
announced topline results from its Phase 2a, randomized,
placebo-controlled, proof-of-concept trial of LYT-300 (oral
allopregnanolone). The trial was designed to evaluate the salivary
cortisol response in the Trier Social Stress Test (TSST), a
validated clinical model of anxiety in healthy volunteers.
This press release features multimedia. View
the full release here:
https://www.businesswire.com/news/home/20231113556006/en/
PureTech announced topline results from
its Phase 2a, randomized, placebo-controlled, proof-of-concept
trial of LYT-300 (oral allopregnanolone). The trial was designed to
evaluate the salivary cortisol response in the Trier Social Stress
Test (TSST), a validated clinical model of anxiety in healthy
volunteers. (Graphic: Business Wire)
Oral administration of LYT-300 achieved the trial’s primary
endpoint of a statistically significant reduction versus placebo in
the increase from baseline to peak levels of the stress hormone
salivary cortisol (p=0.0001). The LYT-300 treatment effect size
versus placebo was 0.72, as measured by Cohen’s d, which is one of
the most common ways to measure effect size. LYT-300 showed a
similar effect size to previously observed results for alprazolam,
a benzodiazepine drug indicated for treatment of anxiety disorders,
when assessed following the TSST procedure2. An increase in
cortisol levels after the TSST is a physiological response and an
objective biomarker of acute stress. Eighty healthy volunteers were
randomized and treated with either LYT-300 or placebo in a 1:1
ratio. LYT-300 was well tolerated, with all treatment-related
adverse events transient, mild or moderate and consistent with the
known pharmacology profile of allopregnanolone. Additional data
from the study will be presented in a scientific forum.
“Anxiety disorders are an area of significant unmet medical need
and current standard-of-care treatments leave much room for
improvement due to inconsistent efficacy and adverse events. We
know that benzodiazepines, like alprazolam, can reduce the salivary
cortisol response to stress in the TSST. Cortisol is an important
marker of the physiological response to stress, and reduction of
stress overreactivity may be an important mechanism for treating
anxiety and stress-related disorders,” said Murray Stein, MD, MPH,
FRCPC, Distinguished Professor of Psychiatry and Public Health at
the University of California San Diego and an advisor to PureTech.
“LYT-300, a non-benzodiazepine neurosteroid, blunts this stress
response, highlighting its novel pharmacology and potential for
helping patients in serious need of new treatment options.”
“These data validate that LYT-300 has potential to make a
difference for people living with anxiety, where there’s been a
dearth of innovation and existing treatments have drawbacks,” said
Daphne Zohar, Founder and Chief Executive Officer of PureTech
Health. “The successful outcome of this trial builds on our
strategy of identifying drugs with proven clinical efficacy but
with historical limitations that have held back their therapeutic
use, and then applying an innovative solution to enhance their
potential for patients. In the CNS arena, we previously applied
this strategy to invent KarXT for the treatment of schizophrenia.
Building on this approach, we now have seven wholly owned CNS
programs powered by our Glyph™ platform, which is designed to
enable the oral bioavailability of drugs with high first-pass
metabolism and resolve hepatotoxicity.”
LYT-300 is an oral prodrug of allopregnanolone, an endogenous
neurosteroid. Allopregnanolone has been recognized for its
potential to treat a range of neurological and neuropsychiatric
indications with a well-established rapid onset of action in mood
disorders. The major hurdles associated with endogenous
neurosteroids in the past have been their lack of oral
bioavailability and inability to chronically administer them to
patients, which means they otherwise can only be administered via a
long, cumbersome intravenous infusion. To overcome the challenges
with this method of administration, medicinal chemistry approaches
have been applied to synthesize orally bioavailable chemical
analogs of allopregnanolone. These oral analogs may have different
pharmacological effects than endogenous allopregnanolone and
therefore may not capture its full therapeutic potential. LYT-300
is designed to achieve oral administration of an endogenous
allopregnanolone that has the potential to capture the breadth of
the natural biological response.
“The data generated with PureTech’s LYT-300 suggest this may be
a promising treatment for anxiety disorders, as well as a range of
related neurological and neuropsychiatric conditions,” said
Maurizio Fava, MD, Psychiatrist-in-Chief at Massachusetts General
Hospital and an advisor to PureTech. “The Glyph platform and the
therapeutic candidates being developed at PureTech have the
potential to treat a range of central nervous system
disorders.”
These results further validate PureTech’s Glyph platform, which
is designed to employ the lymphatic system's natural lipid
absorption and transport process to enable the oral administration
of certain therapeutics that otherwise cannot be administered
orally. PureTech has generated seven CNS programs based on its
Glyph platform, including LYT-300 and LYT-310 (oral cannabidiol),
which is currently in development for the treatment of epilepsies
and other neurological indications.
As part of an overall development strategy in anxiety-related
indications, PureTech will be conducting additional studies in
2024. Further guidance will be provided regarding 2024 catalysts
associated with the planned studies.
About LYT-300 LYT-300 is a clinical-stage therapeutic
candidate that is in development as a potential treatment for
neurological and neuropsychiatric conditions, including anxiety
disorders, mood disorders and Fragile X-associated Tremor/Ataxia
Syndrome. Developed using PureTech’s Glyph™ technology platform,
LYT-300 is an oral prodrug of endogenous allopregnanolone that is
designed to overcome its poor oral bioavailability. PureTech
completed a randomized, placebo-controlled, Phase 2a,
proof-of-concept trial of LYT-300 using a validated clinical model
of anxiety in healthy volunteers in 2023, which demonstrated a
statistically significant reduction in stress response, as measured
by salivary cortisol. PureTech also completed a Phase 1 clinical
trial of LYT-300 in 2022, which demonstrated oral bioavailability,
tolerability and γ-aminobutyric-acid type A (GABAA) receptor target
engagement in healthy volunteers.
About the Glyph™ Platform Glyph is PureTech's
lymphatic-targeting platform which is designed to employ the
lymphatic system's natural lipid absorption and transport process
to enable the oral administration of certain therapeutics. Glyph
reversibly links a drug to a dietary fat molecule, creating a novel
prodrug. The linked fat molecule re-routes the drug's normal path
to the systemic circulation, bypassing the liver and instead moving
from the gut into the lymphatic vessels that normally process
dietary fats. PureTech believes this technology has the potential
to provide a broadly applicable means of enhancing the
bioavailability of certain orally administered drugs that would
otherwise be limited by first-pass liver metabolism. PureTech is
accelerating development of a Glyph portfolio that leverages
validated efficacy, prioritizing highly characterized drugs to
evaluate the ability of the Glyph technology to improve oral
bioavailability or lymphatic targeting. PureTech's lead Glyph
therapeutic candidate, LYT-300 (oral allopregnanolone), completed a
randomized placebo-controlled, Phase 2a, proof-of-concept trial
using a validated clinical model of anxiety in healthy volunteers
in 2023. A Phase 2 clinical trial of LYT-300 in FXTAS in
collaboration with the University of California, Davis, is expected
to initiate in 2024. PureTech has now generated seven CNS programs
based on the Glyph platform. PureTech has a robust intellectual
property (IP) portfolio that includes licensed patents as well as
wholly owned IP, covering the Glyph technology platform, which is
based on the pioneering research of Christopher Porter, PhD, and
his research group at the Monash Institute of Pharmaceutical
Sciences at Monash University. The Porter Research Group and
collaborators have published research in Nature Metabolism,
Angewandte Chemie and the Journal of Controlled Release supporting
the Glyph platform's ability to directly target the lymphatic
system with a variety of therapies.
About the Trier Social Stress Test The Trier Social
Stress Test (TSST; Kirschbaum, Pirke, & Hellhammer, 1993) is a
validated clinical model of anxiety. It is a widely used and
well-established psychological and physiological laboratory test
designed to induce acute psychosocial stress in human participants.
It is considered the gold standard in human experimental stress
research and is used by researchers to investigate how individuals
respond to acute stressors, how stress affects cognitive and
emotional processes, and how stress might contribute to various
psychological and physiological conditions. The TSST puts the
participant in situations designed to elicit unpredictable, novel,
anticipatory, and social stress such as preparing and giving a
speech, performing arithmetic, and being observed by judges. It
models stress reactivity, which is an important component in many
mood, stress and anxiety disorders, and the TSST robustly increases
physiological markers of stress including salivary cortisol.
Benzodiazepines, a clinically effective drug class indicated for
the treatment of anxiety, reliably blunt the increased salivary
cortisol in the TSST.
Juliane Hellhammer, PhD, founder and CEO of daacro (a contract
research organization specialized on psychotropic drug effects) and
recognized expert on the Trier Social Stress Test, is an advisor to
PureTech.
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 27
therapeutics and therapeutic candidates, including two (Plenity®
and EndeavorRx®) that have received both US 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 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 statements that
relate to our expectations around the design of and the timelines
and key milestones associated with clinical trials for LYT-300 and
other programs from the Glyph™ platform, including in
anxiety-related indications, the therapeutic potential of LYT-300,
our expectations regarding the Glyph platform including the
potential for new treatment applications, our therapeutic
candidates and approach towards addressing major diseases, 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, 2022 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.
1] Any Anxiety Disorder. (n.d.). National Institute of Mental
Health (NIMH).
https://www.nimh.nih.gov/health/statistics/any-anxiety-disorder 2]
Psychoneuroendocrinology, 31(10), 1278–1288.
https://doi.org/10.1016/j.psyneuen.2006.09.009 .
View source
version on businesswire.com: https://www.businesswire.com/news/home/20231113556006/en/
PureTech Public Relations
publicrelations@puretechhealth.com Investor Relations
IR@puretechhealth.com
EU Media Ben Atwell, Rob Winder +44 (0) 20 3727 1000
ben.atwell@FTIconsulting.com
U.S. Media Nichole Sarkis +1 774 278 8273
nichole@tenbridgecommunications.com
PureTech Health (NASDAQ:PRTC)
Historical Stock Chart
From Jun 2024 to Jul 2024
PureTech Health (NASDAQ:PRTC)
Historical Stock Chart
From Jul 2023 to Jul 2024