Centessa Pharmaceuticals Announces Preclinical Data Supporting ORX750’s Potential as a Best-in-Class Oral OX2R Agonist for the Treatment of Narcolepsy and Other Sleep-Wake Disorders
25 October 2023 - 11:00PM
Centessa Pharmaceuticals Announces Preclinical Data Supporting
ORX750’s Potential as a Best-in-Class Oral OX2R Agonist for the
Treatment of Narcolepsy and Other Sleep-Wake Disorders
Centessa Pharmaceuticals plc (Nasdaq: CNTA), a clinical-stage
pharmaceutical company that aims to discover and develop medicines
that are transformational for patients, today announced a robust
set of new preclinical data from in vivo and in vitro studies of
its investigational, novel orexin receptor 2 (OX2R) agonist,
ORX750, that support its potential best-in-class profile for the
treatment of narcolepsy and other sleep-wake disorders.
The preclinical data will be featured today in an
oral presentation by Sarah Wurts Black PhD, Head of Biology for
Centessa’s Orexin Agonist Program, entitled, “ORX750, an Oral
Selective Orexin Receptor 2 Agonist, Promotes Wakefulness and
Reduces Cataplexy in the Orexin/Ataxin-3 Mouse,” at the World Sleep
Congress in Rio De Janeiro, Brazil.
“We are very excited to share this robust
preclinical dataset, which we believe shows the significant
activity of low doses of ORX750 in highly predictive, translational
models of narcolepsy type 1 (NT1),” said Mario Alberto Accardi PhD,
President of Centessa’s Orexin Agonist Program. “The preclinical
data showed ORX750 achieved maximal wake times and suppressed
cataplexy at 0.1 mg/kg, the lowest oral dose tested in the DTA
mouse model. Notably, this activity was observed in both the DTA
and Atax mouse models that recapitulate NT1 symptoms in humans. The
data also showed ORX750 significantly increased wake time in
healthy wild type mice at 1 mg/kg, the lowest oral dose tested,
supporting the potential for expansion into broader sleep-wake
disorders with normal orexin tone, including narcolepsy type 2
(NT2) and idiopathic hypersomnia (IH). We believe these data
highlight the breadth of ORX750’s potential as a novel treatment
for individuals living with narcolepsy and other sleep-wake
disorders.”
“ORX750 is a highly potent and selective novel
orexin agonist that closely mimics the function of the endogenous
peptide,” said Saurabh Saha MD PhD, Chief Executive Officer of
Centessa. “These preclinical data showed that ORX750 has the
potential to address the underlying pathophysiology of orexin
neuron loss in NT1 and promote wakefulness during the day and
suppress cataplexy, including at levels that correspond to very low
predicted human doses. In addition, the preclinical pharmacokinetic
(PK) profile of ORX750, informed by PK testing in multiple species,
including non-human primates, suggests the potential for ORX750 to
have high, early and sustained brain exposure. We believe these
data provide a strong translational foundation for clinical
development. We are focused on rapidly moving ORX750 through
IND-enabling studies, obtaining IND clearance and initiating
clinical development of ORX750 with the goal of sharing clinical
proof of concept data in 2024. We look forward to providing further
updates in the coming months.”
Overview of ORX750 Preclinical
Results:
- ORX750 is a full OX2R agonist that potently activated the OX2R
with an in vitro EC50 of 0.11 nM and 9,800-fold selectivity over
the human orexin receptor (hOX1R)1.
- In highly predictive, translational Atax and DTA mouse models,
oral administration of ORX750 showed significant activity at the
lowest dose tested, which was 0.1 mg/kg in a DTA mouse model, 0.3
mg/kg in an Atax mouse model, and 1 mg/kg in healthy wild type
mice. ORX750:
- Achieved maximal (100%) wake time for at least 3 hours
post-dose;2
- Suppressed cataplexy for at least 6 hours post-dose;2
- Increased latency to sleep and cataplexy, which was maintained
for >14 days of dosing;3 and,
- Increased consolidation of wakefulness.4
References: 1. Fluorescent imaging plate reader
(FLIPR) assay with Chinese hamster ovary (CHO) cells stably
expressing recombinant human OX1R or OX2R; OXA EC50 at hOX2R =
0.035 nM. 2. As measured by electroencephalogram (EEG) and
electromyogram (EMG) with concurrent video in DTA and Atax mouse
models. 3. As measured by EEG and EMG with concurrent video in Atax
mouse model. 4. PiezoSleep assay as measured in DTA and Atax mouse
models.
Centessa’s preclinical data presentation for ORX750
will be available within a recorded webcast on the Company’s
website at https://investors.centessa.com/events-presentations
immediately following the World Sleep presentation taking place at
10:45 a.m. BRT / 9:45 a.m. ET.
About ORX750ORX750 is an
investigational, orally administered, highly potent and selective
orexin receptor 2 (OX2R) agonist designed to directly target the
underlying pathophysiology of orexin neuron loss in narcolepsy type
1 (NT1). ORX750 is Centessa’s first orexin product candidate being
developed for the treatment of narcolepsy with potential expansion
into other sleep-wake disorders. ORX750 is currently undergoing
IND-enabling activities and has not been administered as an
investigational drug to humans in any jurisdiction.
About Centessa
PharmaceuticalsCentessa Pharmaceuticals plc is a
clinical-stage pharmaceutical company that aims to discover and
develop medicines that are transformational for patients. Our
programs span discovery-stage to late-stage development and cover a
range of high-value indications. We operate with the conviction
that each one of our programs has the potential to change the
current treatment paradigm and establish a new standard of care.
For more information, visit http://www.centessa.com/, which does
not form part of this release.
Forward-Looking StatementsThis
press release contains forward-looking statements. These statements
may be identified by words such as “may,” “might,” “will,” “could,”
“would,” “should,” “expect,” “intend,” “plan,” “objective,”
“anticipate,” “believe,” “estimate,” “predict,” “potential,”
“continue,” “ongoing,” “aim,” “seek,” and variations of these words
or similar expressions that are intended to identify
forward-looking statements. Any such statements in this press
release that are not statements of historical fact may be deemed to
be forward-looking statements, including statements related to: the
Company’s ability to deliver transformational medicines to
patients; the activity significance of low doses in highly
predictive, translational models of narcolepsy type 1 (NT1)
including maximal wake times and suppressed cataplexy at the lowest
oral dose tested; the Company’s expectations on the timing of
Ind-enabling studies of ORX750 in narcolepsy and other sleep-wake
disorders; the ability of our management team and board to drive
execution of the Company’s portfolio of programs; our asset-centric
business model and the intended advantages and benefits thereof;
the scope, progress, results and costs of developing our product
candidates or any other future product candidates; our current
expectations concerning, amongst other things, the development and
therapeutic potential and benefits of our product candidates,
including ORX750 and other OX2R agonists; strategy; regulatory
matters, including the timing and likelihood of initiating clinical
trials, reporting clinical trial results, ability to initiate or
continue clinical trials or market any products; and the market
size and opportunity for our product candidates.
Any forward-looking statements in this press
release are based on our current expectations, estimates and
projections only as of the date of this release and are subject to
a number of risks and uncertainties that could cause actual results
to differ materially and adversely from those set forth in or
implied by such forward-looking statements. These risks and
uncertainties include, but are not limited to, risks related to the
safety and tolerability profile of our product candidates including
ORX750; our ability to protect and maintain our intellectual
property position; business (including commercial viability),
regulatory, economic and competitive risks, uncertainties,
contingencies and assumptions about the Company; risks inherent in
developing product candidates and technologies; our ability to
obtain adequate financing, including through our financing facility
with Oberland, to fund our planned clinical trials and other
expenses; trends in the industry; the legal and regulatory
framework for the industry, including the receipt and maintenance
of clearances to conduct or continue clinical testing; future
expenditures risks related to our asset-centric corporate model;
the risk that any one or more of our product candidates will not be
successfully developed and/or commercialized; and the risk that the
results of non-clinical studies or clinical studies will not be
predictive of future results in connection with future studies.
These and other risks concerning our programs and operations are
described in additional detail in our Annual Report on Form 10-K,
Quarterly Reports on Form 10-Q, and our other reports, which are on
file with the U.S. Securities and Exchange Commission (SEC). We
explicitly disclaim any obligation to update any forward-looking
statements except to the extent required by law.
Contact: Kristen K. Sheppard,
Esq.SVP of Investor Relations investors@centessa.com
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