TIDMPRTC
PureTech Health PLC
18 November 2020
18 November 2020
PureTech Health plc
PureTech's LYT-100 (Deupirfenidone) Demonstrates Tolerability
and Pharmacokinetic Proof-of-Concept in Phase 1 Multiple Ascending
Dose and Food Effect Study
LYT-100 was well-tolerated at all pre-specified doses, so an
additional cohort of 1000 mg twice a day was added, which was also
well-tolerated
In a previous study, a single dose of 801 mg of LYT-100 yielded
greater exposure than a single dose of 801 mg (FDA-approved dose)
of pirfenidone
LYT-100 to be advanced for conditions involving inflammation and
fibrosis and disorders of lymphatic flow, including idiopathic
pulmonary fibrosis, Long COVID and lymphedema
PureTech Health plc (LSE: PRTC, Nasdaq: PRTC) ("PureTech" or the
"Company"), a clinical-stage biotherapeutics company dedicated to
discovering, developing and commercializing highly differentiated
medicines for devastating diseases, today announced the completion
of a Phase 1 multiple ascending dose and food effect study for
LYT-100 (deupirfenidone). The study demonstrated favorable
proof-of-concept for LYT-100's tolerability and pharmacokinetic
(PK) profile, which will also enable twice-a-day (BID) dosing of
LYT-100 in future studies. LYT-100 is PureTech's wholly-owned
product candidate that is being advanced for the potential
treatment of conditions involving inflammation and fibrosis and
disorders of lymphatic flow.
LYT-100 is a deuterated, oral small molecule designed to
overcome the challenges associated with pirfenidone, an approved
and marketed anti-inflammatory and anti-fibrotic drug. Pirfenidone
is currently approved for the treatment of idiopathic pulmonary
fibrosis (IPF), but it is associated with significant tolerability
issues and dose-limiting toxicities leading approximately 50% of
patients to discontinue use, dose adjust or switch therapies, which
results in suboptimal disease management.[1] LYT-100, a new
chemical entity, retains the pharmacology of pirfenidone but has a
differentiated PK profile, which is designed to enable improved
tolerability, less frequent dosing and potentially increased
efficacy.
"The strong results from this Phase 1 readout reinforce our view
that LYT-100 has the potential to offer a tolerability and
bioavailability profile that could be highly differentiated at the
same exposure levels as pirfenidone," said Daphne Zohar, co-founder
and chief executive officer of PureTech. "Based on these results,
we plan to move the program forward in multiple indications
characterized by inflammation and fibrosis, including IPF, where
pirfenidone is shown to have benefit but where tolerability
concerns have limited its use. We also plan to initiate two trials
evaluating LYT-100 in novel indications such as Long COVID
respiratory complications and related sequelae and lymphedema this
quarter."
Multiple ascending dose and food effect study results
The Phase 1 multiple ascending dose and food effect study was a
randomized, double-blind study designed to evaluate the safety,
tolerability and PK profile of LYT-100 in healthy participants. In
the multiple ascending dose part of the study, participants were
initially scheduled to receive increasing doses of LYT-100 up to
750 mg BID. LYT-100 was well-tolerated at all pre-specified doses,
so an additional cohort receiving 1000 mg BID was assessed. LYT-100
was well-tolerated at that dose as well. In the food effect portion
of the study, participants received a single dose of 500 mg of
LYT-100 with or without food.
All adverse events (AEs) that were possibly or probably related
to LYT-100 were mild and transient and there were no
discontinuations. The most common AEs across all multiple ascending
dose cohorts were headache (23.3% with LYT-100 vs. 20.0% with
placebo), abdominal distension (10.0% with LYT-100 vs. 0% with
placebo), nausea (10.0% with LYT-100 vs. 0% with placebo) and
abdominal discomfort (6.7% with LYT-100 vs. 10.0% with placebo).
The only AEs observed in the highest dose cohort (1000 mg BID) that
were considered possibly related to LYT-100 were two headaches. No
serious AEs or dose-limiting toxicities were observed in the study,
and there was no dose response for any type of AE. The maximum
tolerated dose was not observed during this study, suggesting
higher doses could be explored.
The food effect portion of the study evaluated two common PK
measures that are used to determine the dose of a product candidate
- area under the curve (AUC), which represents exposure, and Cmax,
which reflects the maximum concentration following drug
administration. AUC and Cmax were each observed to decrease when
LYT-100 was taken with food as compared to fasting conditions.
Under fed conditions, the AUC reduction observed with LYT-100 (19%)
was comparable to the AUC reduction stated in the ESBRIET(R)
(pirfenidone) US Prescribing Information (16%). The Cmax reduction
observed with LYT-100 was 23%, while the Cmax reduction stated in
the ESBRIET(R) (pirfenidone) US Prescribing Information is 49%.
Based on the food effect findings, PureTech intends to explore the
use of LYT-100 in future studies without regard to when food is
consumed.
The therapeutic dose of pirfenidone approved by the US Food and
Drug Administration (FDA) for the treatment of IPF is 801 mg three
times a day. LYT-100 is designed to potentially improve upon this
regimen. In a previously conducted, single-dose crossover study, an
801 mg dose of LYT-100 resulted in greater drug exposure than an
801 mg of pirfenidone. In the recently completed Phase 1 study,
LYT-100 was well-tolerated at a dose above 801 mg. These data,
together with PureTech's PK modelling of LYT-100 and pirfenidone
exposures, indicate the potential for twice-a-day dosing with
LYT-100.
Based on these results, PureTech plans to move the program
forward in multiple indications, including IPF, Long COVID, and
lymphedema. This quarter, PureTech plans to initiate a Phase 2
trial evaluating LYT-100 as a potential treatment for Long COVID
respiratory complications and related sequelae and a second Phase
2a proof-of-concept study evaluating LYT-100 in patients with
breast cancer-related, upper limb secondary lymphedema. PureTech is
also advancing LYT-100 for the treatment of IPF and is actively
planning additional PK and dosing studies.
About LYT-100
LYT-100 is PureTech's most advanced wholly-owned product
candidate. A deuterated form of pirfenidone, an approved
anti-inflammatory and anti-fibrotic drug, LYT-100 is being advanced
for the potential treatment of conditions involving inflammation
and fibrosis and disorders of lymphatic flow, including lung
dysfunction conditions (e.g., IPF, unclassifiable interstitial lung
diseases (uILDs), Long COVID respiratory complications and related
sequelae) and lymphedema. PureTech completed a Phase 1 multiple
ascending dose and food effect trial evaluating LYT-100 in healthy
volunteers and found it to be well-tolerated at all doses tested.
In Q4 2020, PureTech plans to initiate a Phase 2 trial evaluating
LYT-100 as a potential treatment for Long COVID respiratory
complications and related sequelae and a Phase 2a proof-of-concept
study evaluating LYT-100 in patients with breast cancer-related,
upper limb secondary lymphedema. PureTech is also advancing LYT-100
for the treatment of IPF and is actively planning additional PK and
dosing studies .
About PureTech Health
PureTech is a clinical-stage biotherapeutics company dedicated
to discovering, developing and commercializing highly
differentiated medicines for devastating diseases, including
intractable cancers, lymphatic and gastrointestinal diseases,
central nervous system disorders and inflammatory and immunological
diseases, among others. 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 24 products and product candidates, including two
that have received FDA clearance and European marketing
authorization. All of the underlying programs and platforms that
resulted in this pipeline of product candidates were initially
identified or discovered and then advanced by the PureTech team
through key validation points based on the Company's unique
insights into the biology of the brain, immune and gut, or BIG,
systems and the interface between those systems, referred to as the
BIG Axis.
For more information, visit www.puretechhealth.com or connect
with us on Twitter @puretechh.
Forward Looking Statement
This press release contains statements that are or may be
forward-looking statements, including statements that relate to the
company's future prospects, developments, and strategies. The
forward looking statements are based on current expectations and
are subject to known and unknown risks and uncertainties that could
cause actual results, performance and achievements to differ
materially from current expectations, including, but not limited
to, our expectations regarding the potential therapeutic benefits
of LYT-100, our plans to initiate a Phase 2 trial evaluating
LYT-100 as a potential treatment for Long COVID respiratory
complications and related sequelae and a Phase 2a proof-of-concept
study evaluating LYT-100 in patients with breast cancer-related,
upper limb secondary lymphedema, our plans to advance LYT-100 for
the treatment of IPF and those risks and uncertainties described in
the risk factors included in the regulatory filings for PureTech
Health plc. 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, neither the company nor any other party intends to
update or revise these forward-looking statements, whether as a
result of new
information, future events or otherwise.
Contact:
Investors EU media US media
Allison Mead Talbot Ben Atwell, Rob Winder Stephanie Simon
+1 617 651 3156 +44 (0) 20 3727 1000 +1 617 581 9333
amt@puretechhealth.com ben.atwell@FTIconsulting.com stephanie@tenbridgecommunications.com
[1] Cottin, V., Koschel, D., Günther, et al. (2018). Long-term
safety of pirfenidone: Results of the prospective, observational
PASSPORT study. ERJ Open Research, 4(4), 00084-2018.
doi:10.1183/23120541.00084-2018
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