Positive data from recent MELAS clinical trials heighten urgency to provide first-ever therapy for patients with rare inherited mitochondrial diseases
Prioritized development programs and organizational structures aligned with mitochondria
Plans to meet with FDA in Q4 2022 to discuss MELAS development program
CAMBRIDGE, Mass., Oct. 06, 2022 (GLOBE NEWSWIRE) — Cyclerion Therapeutics, Inc. (Nasdaq: CYCN) today announced a corporate strategic plan focused on mitochondrial diseases. Encouraged by positive data from the recently completed CY6463 Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-like Episodes (MELAS) clinical trial, we are pleased to announce the first approved medicine for patients suffering from a rare mitochondrial disease. We believe we have a unique opportunity to offer. A family of debilitating, progressive, and ultimately fatal genetic diseases.
“We are inspired by the clinical data generated in the recently reported MELAS study. There are clear drug signals seen in objective measures of disease-related domains, and the safety profile of CY6463 is in line with all Motivated by these compelling data and patient populations in dire need of therapy, we are adapting our strategic mission and reprioritizing our development programs. , is focused on manpower, resources and capabilities to bring this potential treatment to individuals with mitochondrial diseases,” said Peter Hecht, Ph.D., CEO of Cyclerion. . “We look forward to engaging with regulators later this year and sharing a detailed development plan early next year.”
Pipeline, organization, and company development
The company investigated the pharmacology of once-daily sGC stimulation with CY6463 in signal-seeking studies in three patient populations: MELAS, schizophrenia-associated cognitive impairment (CIAS), and Alzheimer’s disease with vascular pathology (ADv). I’ve been investigating. Going forward, Cyclerion will focus the future development of his CY6463 on hereditary mitochondrial diseases and initially focus on the development of his MELAS. MELAS is a rare disease that the company believes is uniquely capable of advancing the program.
Melas: In a 29-day open-label study in patients with MELAS, CY6463 treatment was associated with multiple disease-related effects, including mitochondrial function, inflammation, cerebral blood flow, functional brain connectivity, and visually-evoked brain activation. It was associated with improved biomarkers. These data, coupled with data from preclinical studies of cells in mitochondrial disease patients and zebrafish disease models, support the focus of CY6463 on his MELAS/mitochondrial diseases. The company is currently preparing to meet with the FDA to discuss the CY6463 development program, including next studies and a path to his enrollment in MELAS.
CIA: The company presented encouraging CIAS exploratory data underscored by its strong effects on cognitive performance after just 14 days. Cyclerion believes that its next-generation development candidate, CY3018, has properties that make it particularly suitable for the treatment of CIAS and other neuropsychiatric indications. Cyclerion has completed his CY3018 pre-his IND activities and is looking to secure partnerships or other funding mechanisms to develop the program in the future.
Shorthand: Cyclerion recently restricted enrollment in its ongoing ADv clinical trials. This will further enable us to direct resources to the most urgent priorities at MELAS. Data from his ADv study are expected in the first half of 2023. Findings from this and his previous CY6463 studies can be leveraged to optimize future potential Alzheimer’s disease/vascular dementia research.
Organization: The company’s workforce has been aligned with its mitochondrial disease-focused strategy and has been reduced by approximately 45% to 16 full-time employees. We primarily account for approximately $1.9 million in one-time employee-related expenses that we expect to incur in the fourth quarter of 2022, and we expect to realize annual cash savings of approximately $4.1 million. I’m here.
corporate development: To Support Our Mitochondrial Disease-Focused Strategy, Cyclerion Will Leverage Other Assets Through Licensing And Partnerships, Including CY3018 And Two Additional Oral, Clinical-Stage Peripherally Targeted Compounds, Olinciguat And Praliciguat intend to do something. Extensive IP portfolio with long-term exclusivity. Praliciguat has been licensed to Akebia for kidney disease development and, if successful, will provide development, regulatory and commercial milestones and royalties to Cyclerion. We will similarly seek external partners to advance his CY3018 in neuropsychiatric disorders and olinciguat in serious systemic diseases. In exchange, we offer upfront, milestone and royalty payments as a non-dilutive source of capital.
MELAS is a complex, rare disease that affects multiple organ systems, including the central nervous system, varies in severity, and has no approved treatment. MELAS, one of the most common primary mitochondrial diseases (PMDs), is caused by mitochondrial DNA mutations and results in large clusters of familial cases. It is estimated that about 1 in 4,300 people have her mitochondrial disease and about 80% of those with mitochondrial disease have her CNS symptoms. The unmet needs of MELAS are immense. Symptoms can affect virtually every organ and cause severe fatigue, muscle weakness and pain, along with neurological symptoms such as stroke-like episodes, encephalomyopathy, seizures and headaches. Life expectancy is estimated at approximately 17 years from onset of CNS symptoms. The disease interferes with an individual’s ability to live independently, leading to social isolation and reduced overall quality of life.
CY6463 is the first CNS-penetrating sGC stimulator developed as a symptomatic and potentially disease-modifying therapy for severe CNS-involved 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 important biological functions, including mitochondrial function, neuronal function, inflammation, and vasodynamics. Although we have successfully targeted several drugs in the periphery, this mechanism is still therapeutically underutilized in the central nervous system, where impairment of NO-sGC-cGMP signaling has been reported. It is believed to play an important role in the pathogenesis of many neurodegenerative and neuropsychiatric disorders.As an sGC stimulator, CY6463 acts as a positive allosteric modulator, sensitizing sGC enzymes to NO. , increases the production of cGMP, thereby amplifying endogenous NO signaling. CY6463 may have broad therapeutic potential as a therapy to improve cognition and function in people with severe CNS-involved disease by compensating for deficiencies in NO-sGC-cGMP signaling there is.
About Cyclerion Therapeutics
Cyclerion Therapeutics is a clinical-stage biopharmaceutical company with a mission to develop treatments for mitochondrial diseases, including MELAS. Cyclerion’s lead molecule is CY6463. It is the first of a new class of CNS-penetrating sGC stimulators that modulates key nodes of fundamental signaling networks. The multidimensional pharmacology induced by stimulation of sGC has the potential to affect a wide range of diseases involving the CNS. CY6463 is currently in clinical development in MELAS and has shown rapid improvement across multiple disease-related 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).
Certain matters discussed in this press release are “forward-looking statements.” As the case may be, “anticipate”, “believe”, “may”, “continue”, “estimate”, “expect”, “expect”, “plan”, “intend”, We sometimes use terms such as “may”. To identify these forward-looking statements, we use “may,” “could,” “will,” “should,” “forward-looking statements” that convey uncertainty about future events or outcomes. ” and other words. In particular, the company’s statements regarding the potential of CY6463 in the treatment of CNS disorders, including MELAS and other mitochondrial diseases, the potential for successful development of CY6463, sufficient resources and other capabilities to pursue the development of CY6463; Other trends and potential future results are examples of such forward-looking statements. Forward-looking statements involve risks and uncertainties. This includes our ability to maintain sufficient liquidity and capital resources to pursue our business plans for CY6463 or other products, including, but not limited to, our ability to fund additional clinical trials. not), including but not limited to: our ability to demonstrate the efficacy, safety and therapeutic efficacy of CY6463; The success, timing, and cost of any ongoing or future clinical trials and anticipated clinical trials of current product candidates are not necessarily indicative of or support the final results of any ongoing or subsequent clinical trials. . Clinical trial results do not necessarily represent or support the final results of ongoing or subsequent clinical trials. our ability to seek, obtain, and maintain U.S. Food and Drug Administration (“FDA”) or other regulatory approvals or other actions regarding our product candidates; A company’s ability to successfully defend its intellectual property or obtain the necessary licenses at a cost acceptable to the company. Successful implementation of our research and development programs and collaborations. the success of our existing license agreement with Akebia, and our ability to obtain other license agreements; Market acceptance of our product candidates, if approved. and other factors beyond our control, such as general economic conditions and regulatory developments. Actual results or developments could differ materially from those expressed or implied by such statements due to the factors described herein. Forward-looking statements are made only as of the date of this press release, and the Company may publicly update such forward-looking statements to reflect subsequent events or circumstances. assume no obligations.
Dr. Carlo Tanzi
Kendall Investor Relations
Verge Scientific Communications