TIDMPRTC
PureTech Health PLC
14 February 2023
14 February 2023
PureTech Health plc
PureTech to Advance LYT-300 (Oral Allopregnanolone) for the
Potential Treatment of Anxiety Disorders and Postpartum
Depression
A placebo-controlled, Phase 2a, proof-of-concept, social anxiety
clinical trial in healthy volunteers is expected to begin in the
first half of 2023, with results anticipated by the end of 2023
An open-label, Phase 2a, proof-of-concept clinical trial in
women with postpartum depression is expected to initiate in the
second half of 2023
In a healthy volunteer study, LYT-300 achieved blood levels of
allopregnanolone at or above those associated with therapeutic
effect in postpartum depression [1] and was generally
well-tolerated
Allopregnanolone is a natural neurosteroid with proven efficacy
that is currently only available as a 60-hour intravenous
infusion
PureTech Health plc (Nasdaq: PRTC, LSE: PRTC) ("PureTech" or the
"Company"), a clinical-stage biotherapeutics company dedicated to
changing the treatment paradigm for devastating diseases, today
announced that it will advance LYT-300 (oral allopregnanolone) for
the potential treatment of anxiety disorders and postpartum
depression (PPD). A placebo-controlled, Phase 2a, proof-of-concept,
social anxiety clinical trial in healthy volunteers is expected to
begin in the first half of 2023, with results anticipated by the
end of 2023. An open-label, Phase 2a, proof-of-concept clinical
trial in women with PPD is expected to initiate in the second half
of 2023.
"We believe LYT-300 is the most advanced oral prodrug of natural
allopregnanolone and, as such, has the potential to unlock the full
therapeutic benefit of allopregnanolone," said Julie Krop, M.D.,
Chief Medical Officer at PureTech. "Using our proprietary Glyph(TM)
platform, we have made natural allopregnanolone orally bioavailable
without permanently chemically modifying the natural neurosteroid.
This differentiated approach, which harnesses the validated,
fast-acting efficacy of allopregnanolone, may offer an enhanced
therapeutic benefit to patients with a wide range of neurological
and neuropsychiatric conditions, including anxiety and postpartum
depression."
Social Anxiety Trial Design
The placebo-controlled, Phase 2a, proof-of-concept trial will
evaluate short-term changes in anxiety-related patient reported
outcomes in approximately 50 healthy volunteers. The trial will be
conducted using a validated clinical model that simulates social
anxiety.
Postpartum Depression Trial Design
The open-label, Phase 2a, proof-of-concept trial will evaluate
LYT-300 in a small number of patients with moderate to severe PPD.
It is designed to inform dose selection of LYT-300 in this
population given the known efficacy of allopregnanolone in this
population, and it will evaluate scores on the HAM-D scale as well
as other relevant pharmacodynamic markers.
Topline results from a Phase 1 trial of LYT-300 were announced
in December 2022 and showed that oral administration of LYT-300
achieved blood levels of allopregnanolone at or above those
associated with therapeutic benefit in PPD and ninefold greater
than orally administered allopregnanolone, based on third-party
published data.(1) The results also demonstrated exposure-dependent
target engagement with <GAMMA>-aminobutyric-acid type A
(GABA(A) ) receptors, which have been shown to regulate mood and
other neurological conditions.
Allopregnanolone is a natural neurosteroid with well-validated
biological effects. It has demonstrated a rapid onset of action for
the treatment of depression, as well as the potential to treat
other neurological conditions, including anxiety, but its poor oral
bioavailability has limited its therapeutic potential. The United
States Food and Drug Administration (FDA) has approved a 60-hour
intravenous infusion formulation of allopregnanolone for the
treatment of PPD, though this method of administration has inherent
limitations. To overcome this, oral chemically modified analogs of
allopregnanolone have been developed, though these may not capture
the full therapeutic potential of natural allopregnanolone. To
potentially harness the broad applicability of this natural
neurosteroid through oral administration, PureTech has applied its
Glyph platform, which is designed to enable the oral administration
of certain therapeutics with low oral bioavailability due to first
pass metabolism.
"I am exceptionally proud of the progress we've made with the
Glyph platform, which has yielded two exciting therapeutic
candidates to date, and I believe it will be a rich source of
additional candidates for our Wholly Owned Pipeline going forward,"
said Joe Bolen, Ph.D., a member of PureTech's Research and
Development Committee and recently retired Chief Scientific
Officer. "PureTech's unique model includes moving resources toward
the programs with the most promise. To that end, and with a focus
on translational and clinical work, we have recently deprioritized
our Orasome Technology Platform following a key go/no go
experiment. I look forward to continuing to work with the team as a
member of the R&D Committee to advance big ideas, and I am
honored to be a part of such an innovative organization with a deep
commitment to serving patients in need."
About Anxiety
Anxiety disorders are the most common mental disorder, affecting
nearly 30% of adults. [2] There are several types of anxiety
disorders, including generalized anxiety disorder, panic disorder
and social anxiety disorder. They are characterized by feelings of
excessive fear and may impact a person's ability to function
normally.
About Postpartum Depression
Postpartum depression (PPD) is a debilitating condition that
affects over 400,000 women who have given birth in the United
States. [3] It is characterized by feelings of extreme sadness,
changes in energy, sleep and appetite, and it can impact a mother's
ability to care for her child.
About LYT-300
LYT-300 is a clinical therapeutic candidate that is in
development as a potential treatment for anxiety and postpartum
depression. Developed using PureTech's Glyph(TM) technology
platform, LYT-300 is an oral prodrug of natural allopregnanolone.
An intravenous formulation of allopregnanolone is approved by the
United States Food and Drug Administration and administered as a
60-hour infusion for the treatment of postpartum depression.
PureTech completed a Phase 1 clinical trial of LYT-300 in 2022,
which demonstrated oral bioavailability, tolerability and GABA(A)
receptor target engagement in healthy volunteers. Allopregnanolone
is a positive allosteric modulator of
<GAMMA>-aminobutyric-acid type A (GABA(A) ) receptors and has
been shown to regulate mood and other neurological conditions.
Unlike benzodiazepines, allopregnanolone can provide both transient
and longer-term normalization of overactive neural circuits because
it also acts at GABA receptors outside of synapses. [4] Dual intra-
and extra-synaptic GABA PAMs have been shown to not only improve
sleep, [5] but also mood.(1)
About the Glyph (TM) Platform
Glyph is PureTech's lymphatic-targeting chemistry 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 (1) enable direct
modulation of the immune system via drug targets present in
mesenteric lymph nodes and (2) 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 Phase 1 clinical trial in 2022. A placebo-controlled,
Phase 2a, proof-of-concept, social anxiety clinical trial in
healthy volunteers is expected to begin in the first half of 2023,
with results anticipated by the end of 2023. An open-label, Phase
2a, proof-of-concept clinical trial in women with PPD is expected
to initiate in the second half of 2023. A second therapeutic
candidate, LYT-310 (oral cannabidiol), is expected to enter the
clinic in Q4 of 2023. PureTech has a robust intellectual property
portfolio that includes licensed patents as well as wholly owned
patents, covering the Glyph technology platform, which is based on
the pioneering research of Christopher Porter, Ph.D., 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 PureTech Health
PureTech is a biotherapeutics company dedicated to changing the
treatment paradigm for devastating diseases. The Company has
created a broad and deep pipeline through the expertise of its
experienced research and development team and its extensive network
of scientists, clinicians and industry leaders. This pipeline,
which is being advanced both internally and through PureTech's
Founded Entities, is comprised of 26 therapeutics and therapeutic
candidates, including two (Plenity(R) and EndeavorRx(R)) that have
received both U.S. FDA clearance and European marketing
authorization and a third (KarXT) that will soon be filed for FDA
approval, as of the most recent update by the Company. 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
based on unique insights in immunology and drug development.
For more information, visit www.puretechhealth.com or connect
with us on 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, the therapeutic potential of LYT-300, our expectations
regarding the Glyph(TM) technology platform including the potential
for new treatment applications, the applicability of preclinical
results to human subjects, our product 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, 2021 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
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
[1] Brexanolone NDA 211371 Multi-disciplinary Review and
Evaluation, FDA CDER, 2018.
[2] Any Anxiety Disorder. (n.d.). National Institute of Mental
Health (NIMH).
https://www.nimh.nih.gov/health/statistics/any-anxiety-disorder
[3] Bauman, B. L. (2020, May 15). Vital Signs: Postpartum
Depressive Symptoms and Provider . . . Centers for Disease Control
and Prevention.
https://www.cdc.gov/mmwr/volumes/69/wr/mm6919a2.htm?s_cid=mm6919a2_w
[4] Ghit, A. (2021, August 21). GABAA receptors: structure,
function, pharmacology, and related disorders - Journal of Genetic
Engineering and Biotechnology. SpringerOpen.
https://jgeb.springeropen.com/articles/10.1186/s43141-021-00224-0
[5] Bullock, A. (2021, February 15). Zuranolone as an oral
adjunct to treatment of Parkinsonian tremor: A phase 2, open-label
study. Journal of the Neurological Sciences.
https://www.jns-journal.com/article/S0022-510X(20)30613-4/fulltext
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