Positive Data Published in Alzheimer's Research & Therapy from 12-month Phase 2 Study in Alzheimer's Using Personalized Neuromodulation Therapy; Trial Met All Primary and Key Secondary Endpoints

Yahoo

09-04-2025

Data showed strong separation from placebo and statistical significance in mild-to-moderate patients on key measures including CDR-SB, ADAS-Cog11, ADCS-ADL, and NPI
Personalized Neuromodulation (nDMN) targeting the Default Mode Network slowed Alzheimer's in all 3 clinically measured domains: cognition, function, and behavior—with no serious side-effects
This positive peer reviewed 52-week study builds upon prior positive clinical studies and provides important additional evidence on long-term safety and treatment durability.
CAMBRIDGE, Mass., April 02, 2025--(BUSINESS WIRE)--Sinaptica Therapeutics, Inc., a clinical-stage company leading the development of a new class of personalized neuromodulation therapeutics to treat Alzheimer's and other primary neurodegenerative diseases, today announced that positive results of a 52-week Phase 2 study in Mild-to-Moderate Alzheimer's disease patients conducted by the company's scientific co-founder Dr. Giacomo Koch were published in the peer-reviewed journal Alzheimer's Research & Therapy. The publication is titled, "Effects of 52 weeks of Precuneus rTMS in Alzheimer's Disease Patients: a Randomized Trial."
The data, also presented in a podium session at the Clinical Trials on Alzheimer's Disease (CTAD) conference in October 2024 in Madrid, showed that non-invasive personalized neuromodulation of the Default Mode Network (DMN), a key network in the brain involved in memory and cognition, using rTMS-EEG, met all key endpoints with statistical significance, with no serious side-effects.
"This publication reaffirms our confidence in the potential for our non-invasive precision neuromodulation therapy, nDMN, to slow the impairment of cognitive functions, preserve activities of daily living, and reduce behavioral disturbances in Alzheimer's patients," said Giacomo Koch, MD, PhD, Sinaptica scientific co-founder, Neurologist, Professor of Physiology, University of Ferrara, and Director, Non-Invasive Brain Stimulation Laboratory, Santa Lucia Foundation. "We continue to build on our positive clinical evidence including with a just-initiated Phase 2 study in Early Alzheimer's patients, as well as ongoing preparations to launch a pivotal trial in Mild-to-Moderate patients."
Additional analysis from the study included in the publication showed that propagation of the neuromodulation pulses from the precuneus (the stimulation location) to the medial prefrontal cortex was correlated with the primary outcome measure, CDR-SB, implying that the propagation of the signal throughout known areas of the DMN, confirmed via TMS-EEG, is an important requirement for efficacy.
This now published Phase 2 study was a monocentric, randomized, double-blind, sham-controlled, 52-week trial to determine the safety and efficacy of treatment with personalized neuronavigated repetitive transcranial magnetic stimulation (rTMS) targeting the Default Mode Network, the primary functional brain network impacted by Alzheimer's disease. Additional details on the study design are available in a Sinaptica press release at CTAD.
"These peer reviewed results not only highlight the treatment's durability in all disease domains over one year, but the data also points to the importance of confirming broad network engagement of the DMN by measuring distal evoked potentials via neuronavigated TMS-EEG technology," said Ken Mariash, Sinaptica CEO. "This highly personalized approach ensures the neuromodulation pulses can reach distal targets in the DMN so as to induce widespread neuroplasticity throughout the DMN—and furthermore to personalize the dose for every patient to stay within safe-yet-effective bounds."
Summary of Results
The study showed that personalized neuromodulation of the Default Mode Network (nDMN) had a significant effect on the primary outcome measure, Clinical Dementia Rating Scale–Sum of Boxes (CDR-SB). The estimated mean change in CDR-SB after 52 weeks was 1.36 for rTMS-EEG group (95% confidence interval (CI) [0.68, 2.04]) and 2.45 for sham group (95%CI [1.85, 3.05]), resulting in a statistically significant and clinically meaningful separation of 1.09 points, representing a 44% slowing of Alzheimer's progression over the 12-month study duration.
There were also statistically significant effects for the secondary outcomes ADAS-Cog11, MMSE, ADCS-ADL and NPI scores.
On key functional secondary outcome measure, Activities of Daily Living (ADCS-ADL), patients receiving treatment had retained nearly all activities of Daily Living after 1 year, losing only 1.5 points, whereas the placebo arm lost 11.6 points TMS-EEG showed that rTMS increased functional connectivity within the Default Mode Network, and such increase correlated with the changes in clinical scores as measured by the CDR-SB
The procedure was safe and well tolerated with very few minor adverse events reported.
About the SinaptiStim® SystemThe SinaptiStim® System is an investigational new approach to treating Alzheimer's disease using non-invasive personalized precision neuromodulation. Calibrated to each individual's brain, the therapy is delivered in weekly sessions in a recliner ranging from 20 minutes with the first-generation system to six minutes with the second-generation system. The SinaptiStim system delivers safe, painless, customized neurostimulation technology targeting the Default Mode Network (DMN), an important brain network associated with episodic memory, introspection, and other cognitive functions. The technology was granted Breakthrough Device Designation by the FDA in 2022.
The company is preparing for a pivotal randomized controlled clinical trial in mild-to-moderate Alzheimer's with its first-generation system. In this trial, the treatment will be calibrated quarterly using TMS and EEG concurrently in combination with MRI-guided neuronavigation, which enables the SinaptiStim System to achieve customized precise repeatable targeting and safe-yet-effective dosage for each patient, tracking progress and adjusting over time to achieve the best possible individualized outcomes with its nDMN therapy. The pivotal trial will also be designed to determine the effects of SinaptiStim® System on several biomarkers measuring beta amyloid, phosphorylated tau, neuroinflammation, and synaptic dysfunction.
About Sinaptica TherapeuticsSinaptica Therapeutics is a clinical-stage neuromodulation therapeutics company leading the development of a new class of novel personalized therapeutics to revolutionize the treatment of Alzheimer's and other primary neurodegenerative diseases. The company utilizes a patented non-invasive approach to treating Alzheimer's via precision neurostimulation of a key brain network involved in memory, the Default Mode Network. Sinaptica's scientific co-founders pioneered research on this novel approach which a growing body of evidence indicates can slow disease progression. Sinaptica's mission is to bring a safe, effective, and non-invasive neuromodulation therapy to Alzheimer's patients that can help to significantly slow the progression of cognitive, functional, and behavioral decline. Learn more at sinapticatx.com and follow us on LinkedIn and X @SinapticaTX.
The SinaptiStim® System is for investigational use only. It has not been approved by the U.S. Food and Drug Administration and is not available for commercial sale in any geography.
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