CAMBRIDGE, Mass.--(BUSINESS WIRE)--Cognito Therapeutics, a clinical-stage company developing a new class of disease-modifying digital therapeutics to treat neurodegenerative disorders, announced today positive Phase 2 results showing its digital therapeutic utilizing gamma frequency neuromodulation improved memory, cognition, functional abilities and reduced whole brain atrophy and volumetric loss in patients with mild-to-moderate Alzheimer’s disease (AD).
Gamma frequency neuromodulation is a novel digital therapeutic intervention for AD that utilizes EEG-calibrated auditory and visual stimuli to evoke patient-specific neural activity. The mechanism of action has been demonstrated in numerous preclinical studies, where repeated daily exposure to sensory-evoked gamma oscillations resulted in multiple beneficial effects on AD pathophysiology, including reduced production of soluble and insoluble amyloid-beta, microglia-mediated phagocytosis of amyloid plaques, reduced tau-hyperphosphorylation and improved cognitive function.
The Phase 2 OVERTURE study (NCT-03556280) is a multi-center, randomized controlled clinical trial (RCT) evaluating the safety and efficacy of gamma frequency neuromodulation for a 6-month treatment period in a mild-to-moderate AD population. The study enrolled 76 patients aged 50 or older with mild-to-moderate AD (MMSE 14-26, inclusive), randomized to receive either 40 Hz noninvasive audio-visual or sham stimulation one-hour daily at home over the treatment period.
Over the 6-month treatment period, subjects were regularly evaluated for cognitive, functional, and biomarker changes on multiple validated measures. Functional abilities of patients were measured by Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) scale at baseline and every four weeks during the study period. The study also evaluated changes in functional ability and brain volumetric changes in AD patients with mild to moderate cognitive impairment. Brain volumetric changes were assessed by structural magnetic resonance imaging (MRI), taken at baseline and after six months of treatment.
Gamma frequency neuromodulation was safe and well tolerated. Over the 6-month period, patients in the treatment group (n=33) exhibited a significant 84% slowing of functional decline in ADCS-ADL scores and a significant 83% slowing in the rate of decline based on the Mini-Mental State Examination (MMSE), compared to patients in the placebo group (n=20). Patients in the treatment group (n=30) also demonstrated a significant 61% reduction in whole brain atrophy and volumetric loss associated with AD, compared to placebo group patients (n=19) at 6 months, indicating a potential disease modifying effect via quantitative MRI analysis.
The Phase 2 study met its primary safety and tolerability endpoints, and selected secondary endpoints were significant. The results demonstrate that active treatment with gamma frequency neuromodulation also led to significant benefits in the ability to perform activities of daily living via the ADCS-ADL and cognition via the MMSE, representing important treatment and management objectives for AD patients.
“We’re excited to announce our Phase 2 data, which demonstrated significant improvements in memory, cognition and reductions in brain atrophy and volumetric loss in AD patients who received treatment with gamma frequency neuromodulation compared to placebo,” said Brent Vaughan, CEO of Cognito Therapeutics. “With our recent FDA Breakthrough Device Designation, we look forward to expediting the clinical development of what has the promise to be the first disease-modifying digital therapeutic in Alzheimer’s disease.”
“Our approach has translated into clinical proof of concept by successfully achieving statistically significant results in AD, with a potential for disease modification due to significant reduction of cerebral atrophy and volumetric loss,” said Dr. Tom Megerian, Chief Medical Officer, Cognito Therapeutics. “In addition to improving functional outcomes, memory and cognition, the 61% reduction in loss of whole brain volume in our Phase 2 study addresses key aspects of AD etiology and disease progression. If these results are replicated in our larger, pivotal trial, this will represent a huge medical breakthrough in Alzheimer’s research.”
“The combined clinical and biomarker findings suggest beneficial effects of gamma frequency neuromodulation in AD, which may be facilitated via differentiated pathways compared to traditional pharmacologic approaches,” said Zach Malchano, President, Cognito Therapeutics. “We are excited to advance clinical development of our prioprietary gamma frequency neuromodulation approach as a standalone therapy or in combination with other therapeutics in development for the treatment of Alzheimer’s.”
About Cognito Therapeutics
Cognito Therapeutics is a clinical-stage company developing a pipeline of disease-modifying digital therapeutics that have clinically demonstrated drug-like effects using gamma frequency neuromodulation to treat neurodegenerative disorders including Alzheimer’s disease. The company’s licensed proprietary gamma frequency neuromodulation platform technology, developed by scientific founders at MIT, Professors Li-Huei Tsai and Ed Boyden is a non-invasive therapy utilizing visual and auditory stimulation to treat neurodegenerative diseases. The company is based in Boston and San Francisco. For more information, please visit www.cognitotx.com. Follow us on Twitter at @cognitotx.