Cyclerion Announces CY6463 Clinical Pipeline Progress and Second Quarter 2022 Financial Results
Positive topline results for CY6463 announced in two clinical studies in patients with Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-like episodes (MELAS) and Cognitive Impairment Associated with Schizophrenia (CIAS)
Study in Alzheimer’s Disease with vascular pathology (ADv) enrollment ongoing
“The data generated from our recent CY6463 CIAS and MELAS studies demonstrate highly encouraging therapeutic activity and favorable safety and tolerability in two distinct patient populations. The results from these studies provide further evidence of the pro-cognitive and anti-inflammatory effects of CY6463 observed in preclinical studies and prior clinical trials. We also continue to enroll a Phase 2a study in Alzheimer’s Disease and look forward to seeing topline results in 2023.” said
Clinical Pipeline Updates
- In June, the Company 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). Results from the study were also presented at the
United Mitochondrial Disease Foundation(UMDF) Mitochondrial Medicine 2022 Symposium. In this open-label, single-arm study of the oral, once-daily sGC stimulator in eight adults with MELAS, improvements were seen across a range of assessments, 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. CY6463 was well tolerated with no AEs leading to treatment discontinuation, and pharmacokinetics (PK) were consistent with Phase 1 studies in healthy volunteers.
- In July, the Company announced positive topline data from its clinical study of CY6463 for the potential treatment of Cognitive Impairment Associated with Schizophrenia (CIAS) in individuals with stable schizophrenia on a stable, single, atypical antipsychotic regimen. Study data from the 14-day, double-blind, randomized, placebo-controlled, multiple-ascending-dose study demonstrate a strong effect on cognitive performance after two weeks of 15mg once-daily dosing. Positive movement on inflammatory biomarkers was also observed. Data also demonstrate that CY6463 was safe and well tolerated, with no reports of serious adverse events (SAEs), severe adverse events (AEs), or treatment discontinuation due to AEs.
- In July, the Company announced the appointment of
Steven E. Hyman, M.D., to its Board of Directors effective July 25. Dr. Hymanis a Distinguished Service Professor and the Harald McPike Professor of Stem Cell and Regenerative Biology at Harvard Universityand a Core InstituteMember of the Broad Institute of MIT and Harvard. Dr. Hymanalso serves as Chairman of the Board of Directors of the Charles A. Dana Foundation. He is founder of Emugen Therapeutics, a Director of Voyager Therapeutics and Q-State Biosciences, and serves on the scientific advisory boards of Janssen Pharmaceuticalsand F-Prime Capital.
- The Company continues to enroll its ADv study (NCT04798989), a randomized, placebo-controlled study of oral, once-daily CY6463 over a twelve-week dosing period. Study participants must have confirmed Alzheimer’s disease pathology as assessed by PET or CSF biomarkers, cardiovascular risk factors, as well as mild-to-moderate subcortical small-vessel disease as assessed by MRI. The study will evaluate safety, tolerability, and pharmacokinetics as well as explore the impact of CY6463 on various disease-relevant pharmacodynamic biomarkers (e.g., EEG, MRI, neuroinflammatory biomarkers) and cognitive performance.
Second Quarter 2022 Financial Results
- Cash Position: Cash, cash equivalents, and restricted cash balance on
June 30, 2022was approximately $30.3 million, as compared to approximately $41.1 millionon Mar. 31, 2022.
- Research & Development Expenses: R&D expenses were approximately
$10.2 millionfor the second quarter of 2022, as compared to approximately $12.1 millionfor the second quarter of 2021. The decrease of approximately $1.9 millionwas driven by decreases in facilities and operating costs, partially offset by increases in external research costs and employee-related expenses.
- General and Administrative Expenses: G&A expenses were approximately
$3.5 millionfor the second quarter of 2022, as compared to approximately $6.2 millionfor the second quarter of 2021. The decrease of $2.7 millionwas driven by decreases in facilities and operating costs and employee-related expenses.
- Net Loss: Net loss was approximately
$13.4 millionfor the second quarter of 2022, as compared to $16.2 millionfor the second quarter of 2021.
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.
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.
Forward Looking Statement
Certain 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
Kendall Investor Relations
Source: Cyclerion Therapeutics, Inc.