Cyclerion Therapeutics, Inc. (Nasdaq: CYCN), a clinical-stage
biopharmaceutical company on a mission to develop treatments that
restore cognitive function, today announced positive topline data
from its clinical study of CY6463 for the treatment of Cognitive
Impairment Associated with Schizophrenia (CIAS) in individuals with
stable schizophrenia on a stable, single, atypical antipsychotic
regimen. Data from the 14-day, double-blind, randomized,
placebo-controlled, multiple-ascending-dose study demonstrate that
once-daily CY6463 was safe and well tolerated, with no reports of
serious adverse events (SAEs), severe adverse events (AEs), or
treatment discontinuation due to AEs. Study data demonstrate a
strong effect on cognitive performance after two weeks of 15mg
once-daily dosing. A broad positive movement on inflammatory
biomarkers was also observed. These signals on exploratory
endpoints provide further evidence of the pro-cognitive and
anti-inflammatory effects of CY6463 observed in preclinical studies
and prior clinical trials.
“Cognitive impairment is a central debilitating,
and untreated facet of schizophrenia, and there is a significant
need for a treatment option that improves cognition,” said Steven
E. Hyman, M.D., Core Member of the Broad Institute, Director of the
Stanley Center for Psychiatric Research at the Broad Institute, and
new member of Cyclerion’s Board of Directors. “I am encouraged by
the promising cognition signals observed after only two weeks of
CY6463 dosing in patients with stable schizophrenia. These data
demonstrate the therapeutic potential of amplifying sGC signaling
in the CNS, including positive effects on cognition and
inflammation, and support further development of CY6463 in diseases
characterized by cognitive impairment.”
CY6463 is a positive allosteric modulator of
soluble guanylate cyclase (sGC) that amplifies endogenous nitric
oxide (NO) signaling, a pathway that has been linked to
schizophrenia.
The clinical study enrolled 48 participants with stable
schizophrenia with no more than moderate positive symptoms and on a
stable, single, atypical antipsychotic regimen. Topline results
include:
- CY6463 was safe and well tolerated. There were no reports of
SAEs, severe AEs, or treatment discontinuation due to AEs. All AEs
were transient.
- The pharmacokinetic profile of once-daily CY6463 is consistent
with earlier clinical studies in healthy volunteers and MELAS
patients, and demonstrated linear, dose-proportional exposure and
low intersubject variability.
- The general cognition composite score from the Cogstate
Schizophrenia Battery increased with 14 days of once-daily dosing
with CY6463 15 mg, compared to placebo, with an effect size of
0.60. An effect size of approximately 0.3 is generally considered
clinically relevant in neuropsychiatry.
- Favorable changes were observed in a broad panel of plasma
inflammatory biomarkers, including biomarkers with links to
schizophrenia and cognition, after 14 days of once-daily dosing
with CY6463 15 mg. These anti-inflammatory effects extend results
observed in preclinical and earlier clinical studies of
CY6463.
- Analysis of data from exploratory EEG assessments (resting
state, qEEG, ERP, sleep EEG,) are ongoing. Data from these
assessments will be shared in future scientific forums.
- At the two higher dose levels evaluated in this
multiple-ascending-dose study (30 and 60 mg), CY6463 was observed
to be safe and well tolerated; however, higher doses did not
demonstrate an effect on the general cognition composite at Day 14,
a finding consistent with preclinical experiments.
“This is the second clinical study successfully demonstrating
safety, pharmacokinetics, and therapeutic activity in a patient
population where previous drug development has been very
challenging,” said Andreas Busch, Ph.D., Chief Scientific Officer
at Cyclerion Therapeutics. “These exciting results confirm previous
clinical and preclinical findings, adding to a strong data package
that supports the advancement of CY6463 in CNS diseases where
cognition is impaired, including CIAS and MELAS. We are eager to
build on the momentum from these positive data and continue to
assess opportunities to accelerate development, refine patient
selection, and improve endpoint assessment.”
“The data emerging from this CIAS study, coupled with the
recently reported CY6463 MELAS clinical study data, demonstrate
positive multi-dimensional therapeutic activity and favorable
safety and tolerability in two distinct patient populations,” said
Peter Hecht, Ph.D., Chief Executive Officer of Cyclerion. “These
data present a path and opportunity forward for Cyclerion’s
first-in-class, CNS-penetrant sGC stimulator to yield multiple
breakthrough CNS therapeutics across patient populations in need of
novel treatment options. We continue to explore potential
partnerships with parties who share our vision for the broad
therapeutic potential of sGC in treating CNS disorders.”
Webinar Information The Company will discuss
these positive topline clinical data during a live webinar on
Thursday, July 28th at 8:00 a.m. EDT, including a live Q&A. The
live event can be accessed by visiting the investors' section of
the Cyclerion website at
https://ir.cyclerion.com/news-events/event-calendar. An archived
replay will also be available on the Cyclerion website.
About the CIAS Study
The CIAS trial (NCT04972227) was an in-center, randomized,
placebo-controlled, multiple-ascending-dose study of oral,
once-daily CY6463 in 48 adults aged 18-50 who were diagnosed with
stable schizophrenia with no more than moderate positive symptoms
and on a stable, single, atypical antipsychotic regimen. The
primary objective of the study was to assess the safety and
tolerability of 15, 30 and 60 milligram, once-daily, oral doses of
CY6463 over 14 days. The secondary objectives included
pharmacokinetics and exploratory pharmacodynamic effects. The study
was not powered for hypothesis testing.
About Schizophrenia and CIAS
Schizophrenia is a chronic brain disorder that affects how
patients think, feel, and behave, which may result in
hallucinations, delusions and/or disordered behavior that impairs
daily functioning. Cognitive impairment is a core, debilitating,
and untreated symptom of schizophrenia, with nearly all patients
suffering from some cognitive deficits. There are currently no
approved therapies that specifically improve cognitive
deficits.
About CY6463
CY6463 is the first CNS-penetrant sGC stimulator to be developed
as a symptomatic and potentially disease-modifying therapy for
serious CNS diseases. The nitric oxide (NO)-soluble guanylate
cyclase (sGC)-cyclic guanosine monophosphate (cGMP) signaling
pathway is a fundamental mechanism that precisely controls key
aspects of physiology throughout the body. In the CNS, the
NO-sGC-cGMP pathway regulates diverse and critical biological
functions including neuronal function, neuroinflammation, cellular
bioenergetics, and vascular dynamics. Although it has been
successfully targeted with several drugs in the periphery, this
mechanism has yet to be fully leveraged therapeutically in the CNS,
where impaired NO-sGC-cGMP signaling is believed to play an
important role in the pathogenesis of many neurodegenerative and
neuropsychiatric diseases and other disorders associated with
cognitive impairment. As an sGC stimulator, CY6463 acts as a
positive allosteric modulator to sensitize the sGC enzyme to NO,
increase the production of cGMP, and thereby amplify endogenous NO
signaling. By compensating for deficient NO-sGC-cGMP signaling,
CY6463 and other sGC stimulators may have broad therapeutic
potential as a treatment to improve cognition and function in
people with serious CNS diseases.
About Cyclerion
Therapeutics Cyclerion Therapeutics is a
clinical-stage biopharmaceutical company on a mission to develop
treatments that restore cognitive function. Cyclerion’s lead
molecule is CY6463, a novel, first-in-class, CNS-penetrant, sGC
stimulator that modulates a key node in a fundamental CNS signaling
network. The multidimensional pharmacology elicited by the
stimulation of sGC has the potential to impact a broad range of CNS
diseases. CY6463 has shown rapid improvement in biomarkers
associated with cognitive function and is currently in clinical
development for Alzheimer's Disease with Vascular pathology (ADv)
and Mitochondrial Encephalomyopathy, Lactic Acidosis and
Stroke-like episodes (MELAS) and Cognitive Impairment Associated
with Schizophrenia (CIAS). Cyclerion is also advancing CY3018, a
next generation sGC stimulator.
For more information about Cyclerion, please
visit https://www.cyclerion.com/ and follow us on Twitter
(@Cyclerion) and LinkedIn
(http://www.linkedin.com/company/cyclerion).
Forward Looking StatementCertain matters
discussed in this press release are “forward-looking statements”.
We may, in some cases, use terms such as “predicts,” “believes,”
“potential,” “continue,” “estimates,” “anticipates,” “expects,”
“plans,” “intends,” “may,” “could,” “might,” “will,” “should”,
“positive” or other words that convey uncertainty of future events
or outcomes to identify these forward-looking statements. In
particular, the Company’s statements regarding the potential for
CY6463 in the treatment of CNS diseases, including CIAS and MELAS,
the potential for any successful development of CY6463, the
sufficiency of our resources and other abilities to pursue the
development of CNS, and other trends and potential future results
are examples of such forward-looking statements. The
forward-looking statements include risks and uncertainties,
including, but not limited to, our ability to continue with
sufficient liquidity and capital resources to pursue our business
plan regarding CY6463 or any other product (including without
limitation our ability to fund additional clinical trials); our
ability to successfully demonstrate the efficacy, safety and
therapeutic effectiveness of CY6463; the success, timing and cost
of our ongoing or future clinical trials and anticipated clinical
trials for our current product candidates, including statements
regarding the timing of initiation and completion of the trials,
futility analyses and receipt of interim results, which are not
necessarily indicative of or supported by the final results of our
ongoing or subsequent clinical trials; any results of clinical
studies not necessarily being indicative of or supported by the
final results of our ongoing or subsequent clinical trials;; the
timing of and our ability to pursue, obtain and maintain U.S. Food
and Drug Administration (“FDA”) or other regulatory authority
approval of, or other action with respect to, our product
candidates; the potential for the CY6463 clinical trial to provide
a basis for approval for treatment of MELAS and CIAS; the Company’s
ability to successfully defend its intellectual property or obtain
necessary licenses at a cost acceptable to the Company, if at all;
the successful implementation of the Company’s research and
development programs and collaborations; the success of the
Company’s license agreements; the acceptance by the market of the
Company’s product candidates, if approved; and other factors,
including general economic conditions and regulatory developments,
not within the Company’s control. The factors discussed herein
could cause actual results and developments to be materially
different from those expressed in or implied by such statements.
The forward-looking statements are made only as of the date of this
press release and the Company undertakes no obligation to publicly
update such forward-looking statements to reflect subsequent events
or circumstance.
InvestorsCarlo Tanzi, Ph.D.Kendall Investor
Relationsctanzi@kendallir.com
MediaAmanda SellersVerge Scientific
Communicationsasellers@vergescientific.com
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