Enrollment Begins in Phase 2 Trial for Sinaptica’s Second-Generation Neuromodulation System

Sinaptica Therapeutics Inc.’s second-generation dual stimulation technology is currently being tested in a newly launched, phase 2 double-blind study that will enroll up to 60 early-stage Alzheimer’s patients at multiple centers in Italy.

The second-generation technology builds on the company’s original patented, personalized and precision-delivered rTMS therapy and adds simultaneously delivered transcranial alternating current stimulation. The idea to combine the two modalities was based on over a decade of foundational research conducted by Sinaptica’s scientific co-founders into the mechanisms of memory and methods of potentiating neuroplasticity in the Default Mode Network, including the hippocampus.

This background research recently culminated in a Phase 1 proof-of-concept study in healthy volunteers. Researchers from the Santa Lucia Foundation including lead author and Sinaptica scientific co-founder Dr. Giacomo Koch, investigated this new combined stimulation in various experiments in young healthy volunteers, and were able to demonstrate impressive improvements in long-term associative memory by 60-80% versus controls, with effects durable as long as one week (see published results here).

“We’re continuing to innovate and evolve our precision neuromodulation therapy to provide the most effective and efficient treatment for patients,” said Giacomo Koch, M.D., Ph.D., Sinaptica scientific co-founder, neurologist, professor of Physiology, University of Ferrara, and director, Non-Invasive Brain Stimulation Laboratory, Santa Lucia Foundation. “Our goal with these improvements is to further enhance the overall efficacy of the treatment as well as reduce the time required for each treatment. We hope that this trial will expand the evidence that our neuromodulation of the DMN can be as effective—or even more effective—in early AD, as it has been in mild-to-moderate disease with the first-generation technology, published in the journal BRAIN.”

Dr. Koch and the Santa Lucia Foundation received a €1 million grant from the Italian Ministry of Health to fund this multi-center phase 2 study.

“This next-gen approach incorporating simultaneous stimulation has the potential to act as a future upgrade to our current therapy for Alzheimer’s and is covered by our existing patents. It’s part of our product roadmap in Alzheimer’s, other neurodegenerative diseases, and potentially in memory enhancement for healthy aging,” Sinaptica CEO Ken Mariash stated. “We have a long-term vision for the trajectory of the SinaptiStim system that allows for increased treatment capacity, ongoing enhancement of the patient experience and continual improvements in treatment efficacy.”

The 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 and introspection. The technology was granted Breakthrough Device Designation by the U.S. Food and Drug Administration (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 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, neural inflammation, and synaptic dysfunction.

Sinaptica’s co-founder presented positive Phase 2 data after 12 months using the first-generation system showing strong statistically significant slowing of Alzheimer’s disease progression in mild-to-moderate patients on all key gold-standard measures in all three domains: cognition, function, and behavioral disturbances (CDR-SB, ADAS-COG11, MMSE, ADCS-ADL, and NPI). These successful results were accomplished with no serious side effects.

Sinaptica Therapeutics is a clinical-stage neuromodulation therapeutics company developing a new class of 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.

The SinaptiStim System is for investigational use only. It has not been approved by the FDA and is not available for commercial sale in any geography.