Data from an eight-patient, open-label study demonstrate improvements across multiple biomarkers of mitochondrial function, inflammation, cerebral blood flow, and functional connectivity
CY6463 was well tolerated, with no reports of serious adverse events (SAEs) or treatment discontinuation due to adverse events (AEs); oral, once-daily administration provided expected CNS exposure
Data support further development of CY6463 in CNS diseases with mitochondrial dysfunction
CAMBRIDGE, Mass., June 10, 2022 (GLOBE NEWSWIRE) -- 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 in its signal-seeking clinical study of CY6463, for the potential treatment of Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-like episodes (MELAS). Chad Glasser, Pharm.D., Director of Clinical Research at Cyclerion Therapeutics, will present results from this clinical study today during the Clinical Trial Updates Panel at the United Mitochondrial Disease Foundation (UMDF) Mitochondrial Medicine 2022 Symposium, taking place June 8-11, 2022, in Phoenix, Arizona.
CY6463 is a positive allosteric modulator of soluble guanylate cyclase (sGC), which amplifies endogenous NO signaling, a pathway that has been linked to mitochondrial biogenesis and function. In this open-label, single-arm study of the oral, once-daily sGC stimulator in eight MELAS patients, improvements were seen across a range of biomarkers, including mitochondrial disease-associated biomarkers such as lactate and GDF-15, a broad panel of inflammatory biomarkers, cerebral blood flow, and functional connectivity between neural networks. These positive effects after 29 days of dosing were supported by correlations across several endpoints and were more pronounced in patients with greater baseline disease burden. A return toward baseline levels after discontinuation of CY6463 dosing across several biomarkers was also observed.
CY6463 was well tolerated with no adverse events leading to treatment discontinuation, and pharmacokinetics (PK) were consistent with the Phase 1 study in healthy volunteers. The positive data from this study further support the potential of CY6463, the first and only CNS-penetrant sGC stimulator in clinical development, to provide therapeutic benefit to people living with MELAS.
"MELAS patients currently have no approved treatment options for a devastating orphan disease that affects multiple organs, including the CNS, skeletal muscle, and eyes," said Peter Hecht, Ph.D., Chief Executive Officer of Cyclerion. "We are excited by the strength of these data and consistency across disease domains, which support the further advancement of CY6463 as a potential treatment option."
- The single-arm, open-label study enrolled eight participants who spanned a range of disease burden; 6 of the 8 (75%) were also taking a daily regimen of oral arginine or citrulline, precursors to nitric oxide that are current standard of care for MELAS patients.
- CY6463 was well tolerated; there were no reports of serious adverse events (SAEs) or treatment discontinuation due to adverse events (AEs).
- The PK profile and concentrations in the cerebrospinal fluid (CSF) and plasma were consistent with exposures observed in Phase 1 healthy volunteer studies.
- Effects were observed across multiple domains of disease activity:
- Improvements in biomarkers associated with mitochondrial function including lactate and GDF-15. These changes correlated with each other and with CY6463 plasma concentrations
- Improvements across a broad panel of inflammatory biomarkers
- Increases in cerebral blood flow across all brain regions. These changes correlated with clinical improvement as assessed by the patient global impression of change (PGIC) scale
- Increases in functional connectivity between brain regions and activation of occipital brain regions in response to the visual stimulus as measured by fMRI BOLD
"In this study we saw positive impacts on important biomarkers associated with MELAS and other mitochondrial disease following 29 days of once-daily dosing with CY6463," said Andreas Busch, Ph.D., Chief Scientific Officer at Cyclerion Therapeutics. "These findings are exciting as we think about the potential of our mechanism in mitochondrial disease and more broadly about the effects of CY6463 on mitochondrial function, which is relevant to numerous CNS diseases, including schizophrenia and Alzheimer's Disease."
A video presentation of the topline data is available on the Investor page of the Cyclerion website. Additional data from the MELAS clinical study will be shared in the coming weeks.