TIDMPRTC
PureTech Health PLC
01 August 2023
1 August 2023
PureTech Health plc
PureTech Awarded up to $11.4 Million from U.S. Department of
Defense to Advance LYT-300 (Oral Allopregnanolone) for Fragile
X-associated Tremor/Ataxia Syndrome
Planning underway for Phase 2 trial of LYT-300 in Fragile
X-associated Tremor/Ataxia Syndrome
LYT-300 is also being evaluated in a Phase 2a trial for anxiety
disorders, and a Phase 2a in patients with postpartum depression is
planned to initiate in second half of 2023
LYT-300, LYT-310 and additional preclinical programs for CNS
indications have been produced from PureTech's Glyph(TM) technology
platform for enhancing oral bioavailability
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 that the company has been awarded up to $11.4 million
from the U.S. Department of Defense (DoD) to advance its
therapeutic candidate, LYT-300 (oral allopregnanolone), for the
treatment of Fragile X-associated Tremor Ataxia Syndrome (FXTAS).
The funds will support a Phase 2 trial of LYT-300 in collaboration
with the University of California, Davis (UC Davis).
LYT-300, an oral prodrug of allopregnanolone, is PureTech's
wholly-owned therapeutic candidate for the potential treatment of
anxiety disorders, postpartum depression, FXTAS and other
neurological and neuropsychiatric indications. LYT-300 was
developed using PureTech's Glyph(TM) platform, which harnesses the
body's natural lipid absorption and transport process to enable the
oral administration of certain therapeutics that otherwise cannot
be administered orally.
FXTAS, which was discovered by Dr. Randi Hagerman and her
colleagues at the University of California, Davis, is a devastating
neurological condition that is closely related to, but distinct
from, Fragile X syndrome (FXS). Both conditions are the result of
repeated elements in the Fragile X Messenger Ribonucleoprotein Gene
1 (FMR1) gene. While FXS is associated with intellectual disability
and autism, FXTAS leads to neurodegeneration in otherwise normally
developed, aging individuals who carry a premutation of the FMR1
gene.
"FXTAS is a devastating, late-onset neurodegenerative condition
characterized by cognitive decline, tremors in the hands and
balance problems. Currently, there are no primary treatments for
FXTAS, though IV-administrated allopregnanolone has demonstrated
therapeutic potential," said Dr. Randi Hagerman, M.D., F.A.A.P.,
Medical Director of the UC Davis MIND Institute , Chair in Fragile
X Research and co-primary investigator for the LYT-300 trial. "I am
excited to be working with PureTech to evaluate their oral prodrug
of allopregnanolone (LYT-300), and I am optimistic that this award
will help accelerate the development of this potential first
therapy for FXTAS."
An exploratory, open-label trial of six men with FXTAS,
evaluated IV-administration of allopregnanolone across multiple
neuropsychological and emotional tests. In addition to being
well-tolerated, allopregnanolone showed signals of pharmacologic
benefit across multiple neurological endpoints, including the
Behavioral Dyscontrol Scale, which measures executive, cognitive
and motor function, and demonstrated improvement compared to
baseline (p=0.009). ([1]) IV administration is not feasible in most
indications, especially for a chronic therapy, and there remains a
need for treatments that can address this debilitating condition.
PureTech plans to evaluate LYT-300 in a placebo-controlled trial to
demonstrate the safety, tolerability and efficacy of the drug in
people with FXTAS.
"This award from the DoD allows us to expand our evaluation of
LYT-300, a candidate with a wide variety of potential indications,
into FXTAS, an area of tremendous need where otherwise normally
developed, aging individuals suffer from significant
neurodegeneration," said Eric Elenko, Ph.D., Chief Innovation
Officer at PureTech Health. "We look forward to collaborating with
Dr. Randi Hagerman and her team at UC Davis to bring the potential
of allopregnanolone to the thousands of individuals with FXTAS in
need of a treatment."
PureTech's capital efficient strategy includes the pursuit of
non-dilutive funding in the form of grants. This is the fourth DoD
grant that PureTech has secured on behalf of its Wholly Owned
Programs in addition to five grants secured on behalf of its
Founded Entities. This work is supported by the Office of the
Assistant Secretary of Defense for Health Affairs and the Defense
Health Agency J9, Research and Development Directorate, or the U.S.
Army Medical Research Acquisition Activity at the U.S. Army Medical
Research and Development Command through the Peer Reviewed Medical
Research Program (PRMRP) under Award No. HT94252310598, with a
total program budget of up to $11.4 million for both the planning
and clinical study phases. The PRMRP supports research across the
full range of science and medicine, with an underlying goal of
enhancing the health, care and well-being of military service
members, veterans, retirees and their family members. Opinions,
interpretations, conclusions and recommendations are those of the
author and are not necessarily endorsed by the Department of
Defense.
In addition to LYT-300, which is being advanced in three
indications, PureTech is progressing multiple CNS-focused programs
derived from its Glyph platform. These include LYT-310, an oral
form of cannabidiol that is expected to enter a Phase 1 clinical
trial in the fourth quarter of 2023, as well as programs that are
in various stages of preclinical development.
About Fragile X-associated Tremor/Ataxia Syndrome
Fragile X-associated Tremor/Ataxia Syndrome (FXTAS) was
discovered at the MIND Institute by researcher Dr. Randi Hagerman
and her colleagues in 2001. It is one of the most devastating of
the Fragile X Spectrum Disorders, which result from a trinucleotide
expansion in the FMR1 gene. FXTAS is a late onset condition that
can occur in up to 75% of males with the premutation by the eighth
decade of life and in approximately 16% of females, but the
clinical signs typically emerge when individuals are in their early
60s. The clinical features of FXTAS include tremor in the hands
with action or at rest, balance problems (ataxia) that lead to
frequent falling, and cognitive decline that is sometimes
misdiagnosed as Alzheimer's disease. No specific treatment for
FXTAS is efficacious, though a variety of medications may improve
psychiatric issues or the severity of tremor. Carriers are common
in the general population, occurring in 1 in 150 to 200 women and 1
in 400 men, but FXTAS is often mistakenly diagnosed as Parkinson's
disease.
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,
postpartum depression and Fragile X-associated Tremor/Ataxia
Syndrome. Developed using PureTech's Glyph(TM) technology platform,
LYT-300 is an oral prodrug of endogenous allopregnanolone that is
designed to overcome its poor oral bioavailability. PureTech
completed a Phase 1 clinical trial of LYT-300 in 2022, which
demonstrated oral bioavailability, tolerability and
<GAMMA>-aminobutyric-acid type A (GABA(A) ) receptor target
engagement in healthy volunteers.
Allopregnanolone is a positive allosteric modulator (PAM) of
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. ([2]) An intravenous formulation of
allopregnanolone is approved by the U.S. Food and Drug
Administration as a 60-hour infusion for the treatment of
postpartum depression, though the method of administration has
significant challenges and limits the scope of clinical translation
with this class of compounds. To overcome this, 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.
About the Glyph(TM) 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 (1) provide a broadly
applicable means of enhancing the bioavailability of certain orally
administered drugs that would otherwise be limited by first-pass
liver metabolism and (2) enable direct modulation of the immune
system via drug targets present in mesenteric lymph nodes. 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 trial using a validated clinical model of anxiety
in healthy volunteers initiated in June 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 and planning is
underway for a Phase 2 clinical trial in FXTAS. A second
therapeutic candidate, LYT-310 (oral cannabidiol), is expected to
enter the clinic in Q4 of 2023.
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, 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 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(R) and EndeavorRx(R)) that have received
both US FDA clearance and European marketing authorization and a
third (KarXT) that is expected to be filed soon 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 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, including for FXTAS, 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, 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.
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] Wang, J., Trivedi, A. M., Carrillo, N. R., Yang, J.,
Schneider, A., Giulivi, C. R., Adams, P. D., Tassone, F., Kim, K.,
Rivera, S. M., Lubarr, N., Wu, C. Y., Irwin, R. S., Brinton, R. D.,
Olichney, J. M., Rogawski, M. A., & Hagerman, R. J. (2017).
Open-Label Allopregnanolone Treatment of Men with Fragile
X-Associated Tremor/Ataxia Syndrome. Neurotherapeutics, 14(4),
1073-1083. https://doi.org/10.1007/s13311-017-0555-6
[2] 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
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