Cyclerion Announces CY6463 Clinical Pipeline and Corporate Updates
Phase 2a study in Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) enrollment closed; topline data expected in Q2 2022
Phase 1b study in Cognitive Impairment Associated with Schizophrenia (CIAS) enrollment ongoing; topline data expected in H2 2022
Phase 2a study in Alzheimer’s Disease with vascular pathology (ADv) enrollment ongoing
“We are developing CY6463 as a potentially transformative medicine for cognitive impairment associated with certain CNS diseases that are lacking effective therapies today. The development strategy for this lead program is guided by a robust neuroinnovation engine, designed to identify the patient populations mostly likely to benefit from our treatments,” said
Clinical Pipeline Updates
Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes (MELAS)
The Phase 2a MELAS trial (NCT04475549) is an open-label, single-arm study of oral, once-daily CY6463 in adults aged 18 or older with MELAS. The study includes measures of safety, tolerability, pharmacokinetics, and exploratory pharmacodynamic effects, including MRI and various disease-relevant biomarkers. Study enrollment has closed and topline data are expected in Q2 2022.
Cognitive Impairment Associated with Schizophrenia (CIAS)
The Phase 1 CIAS trial (NCT04972227) is a randomized, placebo-controlled, multiple-ascending-dose study of oral, once-daily CY6463 in adults aged 18-50 diagnosed with schizophrenia. The study includes measures of safety, tolerability, pharmacokinetics, and pharmacodynamics, including a broad battery of EEG-based assessments and a computerized battery of cognitive performance tests. Clinical sites are actively enrolling study participants and topline data are expected in H2 2022.
Alzheimer’s disease with vascular pathology (ADv)
The Phase 2a ADv trial (NCT04798989) is 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. The ADv study has initiated, and enrollment is ongoing.
- Cyclerion and Ariana Pharma announced an artificial intelligence-driven, precision medicine collaboration to identify patient-selection biomarkers in neurological and neuropsychiatric diseases associated with cognitive impairment. The collaboration aims to guide and accelerate the clinical development of Cyclerion’s investigational therapeutics.
Bruce Kinon, MD has joined Cyclerion as Vice President, Clinical Development and is leading the ongoing CY6463 clinical efforts. Dr. Kinonhas been a clinical leader in both academic research and the pharmaceutical industry, at Eli Lilly and Company and Lundbeck Pharmaceuticals LLC, for the development of innovative drug treatments for neuropsychiatric disorders and their effective delivery into clinical practice. He received his M.D. and psychiatry training at the New York University-Bellevue Hospital Medical Centerin New York City.
- Cash, cash equivalents, and restricted cash balance on
December 31, 2021was approximately $54 million, as compared to approximately $63 millionon September 30, 2021.
- Research and development expenses were approximately
$37.6 millionfor the full year 2021, as compared to approximately $56.4 millionfor the full year 2020. The decrease of approximately $18.8 millionwas driven by decreases of approximately $16.1 millionin salaries and other employee-related expenses and approximately $9.2 millionof facilities and operating costs, partially offset by increases of approximately $4.2 millionrelated to a non-cash write-off of leasehold improvements and approximately $2.3 millionin CY3018 external research costs.
- General and administrative expenses were approximately
$20.6 millionfor the full year 2021, as compared to approximately $28.8 millionfor the full year 2020. The decrease of approximately $8.2 millionwas driven by decreases of approximately 5.4 million in salaries and other employee-related expenses, approximately $2.0 millionin facilities and operating costs, and approximately $2.9 millionin outside professional and corporate expenses, partially offset by an increase of approximately $2.1 millionrelated to a non-cash write-off of leasehold improvements.
- Net Loss: Net loss was approximately
$51.6 millionfor the full year 2021, as compared to $77.8 millionfor the full year 2020.
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.
Forward Looking Statement
This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Our forward-looking statements are based on current beliefs and expectations of our management team that involve risks, potential changes in circumstances, assumptions, and uncertainties, including statements about the anticipated timing of release of topline results of our clinical trials; the progression of our clinical programs; and the business and operations of the Company. We may, in some cases use terms such as “predicts,” “believes,” “potential,” “continue,” “anticipates,” “estimates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “likely,” “will,” “should” or other words that convey uncertainty of the future events or outcomes to identify these forward-looking statements. Each forward-looking statement is subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such statement. Applicable risks and uncertainties include the risks listed under the heading “Risk Factors” and elsewhere in our 2021 Form 10-K filed on February 24, 2022, and our subsequent
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Source: Cyclerion Therapeutics, Inc.