Cyclerion Therapeutics, Inc. (Nasdaq: CYCN) today announced its
mitochondrial disease-focused corporate strategic plan. Propelled
by the positive data from the recently completed CY6463
Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-like
episodes (MELAS) clinical study, the Company believes it has a
unique opportunity to deliver the first-ever approved medicine for
patients suffering from rare mitochondrial diseases, a family of
debilitating, progressive, and ultimately fatal genetic diseases.
“We are inspired by the recently reported
clinical data generated in our MELAS study; there is a clear drug
signal seen in objective measures of disease-relevant domains and
the CY6463 safety profile has been favorable across all clinical
studies to date. Motivated by these compelling data and by a
patient population in desperate need of therapies, we are adapting
our strategic mission, reprioritizing our development programs and
focusing our people, resources, and capabilities to deliver this
potential therapy to individuals living with mitochondrial
diseases,” said Peter Hecht, Ph.D., Chief Executive Officer of
Cyclerion. “We look forward to discussions with regulators later
this year, and then sharing more detailed development plans early
in the new year.”
Pipeline, organization, and corporate
development
The company has been exploring the pharmacology
of sGC stimulation with once-daily CY6463 in signal-seeking studies
in three patient populations: MELAS, Cognitive Impairment
Associated with Schizophrenia (CIAS), and Alzheimer's Disease with
Vascular Pathology (ADv). Going forward, Cyclerion will focus
future development of CY6463 on genetic mitochondrial diseases,
concentrating first on development in MELAS, a rare disease where
the company believes it has the capabilities to advance the program
independently.
MELAS: In an open-label, 29-day
study in patients with MELAS, CY6463 treatment was associated with
improvements in multiple disease-relevant biomarkers: mitochondrial
function, inflammation, cerebral blood flow, functional brain
connectivity, and visually evoked brain activation. These data
coupled with data from preclinical studies in cells from
mitochondrial disease patients and in zebrafish disease models
support a focus on MELAS/mitochondrial diseases for CY6463. The
Company is currently preparing to meet with FDA to discuss the
CY6463 development program, including the next study and paths to
registration in MELAS.
CIAS: The company has presented
encouraging CIAS exploratory study data, highlighted by the strong
effect on cognitive performance after only 14 days. Cyclerion
believes its next-generation development candidate, CY3018, has
attributes that make it especially well suited for treating CIAS
and other neuropsychiatric indications. Cyclerion is completing
pre-IND activities for CY3018 and is looking to secure a
partnership or other funding mechanism to develop the program in
the future.
ADv: Cyclerion recently capped
enrollment of its ongoing ADv clinical study. This will further
enable the Company to channel its resources to its most urgent
priorities in MELAS. Data from the ADv study are expected in the
first half of 2023. Learnings from this and previous CY6463 studies
can be leveraged to optimize future potential Alzheimer’s
Disease/Vascular Dementia studies.
Organization: The Company’s
workforce is being tailored to the mitochondrial disease-focused
strategy, leading to a reduction of approximately 45%, to 16
full-time employees. The Company expects to take an aggregate
charge for one-time employee-related costs of approximately $1.9
million that is expected to be incurred primarily in Q4 2022 and
realize annual cash savings of approximately $4.1 million.
Corporate Development: To
support the Company’s mitochondrial disease-focused strategy,
Cyclerion intends to leverage its other assets through
out-licensing and partnerships, including CY3018 and two
additional, oral, clinical-phase, peripherally targeted compounds,
olinciguat and praliciguat, for which the Company has an extensive
IP portfolio with long-duration exclusivity. Praliciguat has been
licensed to Akebia for development in renal diseases and, if
successful, will provide Cyclerion with development, regulatory,
and commercial milestones as well as royalties. The Company will
similarly seek an external partner to advance CY3018 in
neuropsychiatric diseases and olinciguat in serious systemic
diseases in return for a mix of upfront, milestone, and royalty
payments as a source of non-dilutive capital.
About MELASMELAS is a complex
orphan disease affecting multiple organ systems, including the CNS,
with different degrees of severity, and no approved therapies.
MELAS, one of the most common primary mitochondrial diseases
(PMDs), is caused by mitochondrial DNA mutations resulting in large
clusters of familial cases. It is estimated that about 1 in 4,300
individuals has a mitochondrial disease, and ~80% of individuals
with mitochondrial disease have CNS symptoms. The unmet need in
MELAS is immense, symptoms can affect virtually any organ and cause
intense fatigue, muscle weakness, and pain in addition to
neurological manifestations, including stroke-like episodes,
encephalomyopathy, seizures, and headaches. Life expectancy is
estimated at ~17 years from onset of CNS symptoms. The disease
impedes the individual’s ability to live independently and leads to
social isolation and overall reduced quality of life.
About CY6463CY6463 is the first
CNS-penetrant sGC stimulator to be developed as a symptomatic and
potentially disease-modifying therapy for serious diseases that
involve the CNS. 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
mitochondrial function, neuronal function, inflammation, 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. 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 may have broad therapeutic
potential as a treatment to improve cognition and function in
people with serious diseases that involve the CNS.
About Cyclerion
TherapeuticsCyclerion Therapeutics is a clinical-stage
biopharmaceutical company on a mission to develop treatments for
mitochondrial diseases, including MELAS. Cyclerion’s lead molecule
is CY6463, a novel, first-in-class, CNS-penetrant sGC stimulator
that modulates a key node in a fundamental signaling network. The
multidimensional pharmacology elicited by the stimulation of sGC
has the potential to impact a broad range of diseases that involve
the CNS. CY6463 is currently in clinical development for MELAS
where it has shown rapid improvement in multiple disease-relevant
biomarkers. For more information about Cyclerion, please visit
https://www.cyclerion.com/ and follow us on Twitter (@Cyclerion)
and LinkedIn (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 MELAS and other mitochondrial diseases, the
potential for any successful development of CY6463, the sufficiency
of our resources and other abilities to pursue the development of
CY6463, 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
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 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 existing license
agreement with Akebia and the ability to obtain any other 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
Cyclerion Therapeutics (NASDAQ:CYCN)
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