Spinogenix, Inc. recently announced encouraging  results from its completed Phase 2a trial evaluating Tazbentetol (formerly named SPG302) for the treatment of Alzheimer’s disease (AD). Once-daily treatment with Tazbentetol, a first-in-class synaptic regenerative investigational therapy with the potential to reverse cognitive decline, demonstrated early and continued improvement in multiple measures of cognition.

The randomized, double-blind, placebo-controlled Phase 2a study (NCT06427668) enrolled 24 patients in Australia to assess the safety, tolerability, and clinical efficacy of Tazbentetol. Participants with mild-to-moderate AD, defined by a standardized mini mental status exam (MMSE) score between 16 and 26, were given Tazbentetol (300mg or 150mg) daily for up to 24 weeks, beginning with a four-week placebo-controlled period. The study’s primary endpoints included SMMSE, Clinical Dementia Rating Sum of Boxes (CDR-SB), Activities of Daily Living (ADL) and neurophysiological EEG biomarker measures of AD-related brain activity. Participants had the option to remain on treatment past the open label period for an additional 52 weeks at 300mg QD.

Topline results for the 300mg dose from the completed trial, presented at the Clinical Trials on Alzheimer’s Disease (CTAD) conference on December 4, 2025, demonstrated:

• Favorable Safety Profile: Tazbentetol showed a favorable safety profile with no severe or treatment-related adverse events and was well tolerated by participants taking the drug both as a monotherapy and in combination with standard of care therapy.
• Rapid Cognitive Gain: Participants displayed evidence of early cognitive benefits, with a >2.5 point average increase in SMMSE within four weeks vs. placebo (p < 0.05).
• Sustained Improvement: Durable cognitive improvement was observed through the 24-week open-label period in the SMMSE, CDR-SB and ADL outcomes.
• Increasing Benefit Over Time: Scores on the CDR-SB and ADL outcome measures continued to improve over baseline through 40 weeks.
• Objective Neurophysiological Biomarker Evidence of Synaptic Regeneration: Treatment with 300mg Tazbentetol was associated with a significant improved effect in AD-related brain activity patterns as assessed by EEG, including a reversal of established metrics of cortical “slowing” across multiple frequency bands.

The rapid and sustained effects of Tazbentetol on clinical outcome measures are consistent with findings from a NIH-supported, published Alzheimer’s mouse model study where synapse loss in the hippocampus, a key area for memory formation, and cognition, were improved within weeks of daily dosing (Trujillo-Estrada et al, 2021).

“We are highly encouraged by these results, which show the potential impact that a synaptic regenerative therapy can play in helping restore cognitive function in those with Alzheimer’s disease,” said Dr. Stella Sarraf, Chief Executive Officer and Founder of Spinogenix. “With our IND cleared in the U.S., we are looking forward to continuing global development of this first-in-class, and potentially transformative investigational treatment.”

AD is the most common cause of dementia, accounting for 60-70% of cases worldwide. Loss of synapses occurs very early in the disease’s progression and is a major driver of cognitive decline and memory loss.

“This Phase 2a study of Tazbentetol shows encouraging results for synaptic regeneration as a new treatment paradigm in Alzheimer’s,” said Professor Bruce Brew, MD, DSc, FRACP, FAAN, neurologist and principal investigator at St. Vincent’s Hospital in Sydney, Australia who presented at CTAD. “These results show Tazbentetol’s early potential to deliver rapid and sustained cognitive improvement as measured by SMMSE and CDR-SB. The study’s quantitative and qualitative measurements reinforce the importance of reversing synapse losses as a new treatment paradigm that could be initiated following a routine cognitive assessment.”

Tazbentetol offers the potential first synaptic regenerative approach to treating AD with the potential to improve cognition and quality of life. It represents a new class of regenerative therapeutics that can be used in combination with standard-of-care cholinesterase inhibitors, as well as recently approved antibody therapies targeting amyloid beta. Earlier this year, the FDA cleared Spinogenix’s Investigational New Drug (IND) application for Tazbentetol for the treatment of people with AD.

Tazbentetol (formerly SPG302) is a once-a-day pill being developed as a regenerative treatment for neurodegenerative and neuropsychiatric diseases with the unique ability to restore synapses, the key connections between neurons that allow people to think, plan, remember, and control movement. The preliminary evidence of the synaptic regenerative activity of Tazbentetol represents a first-in-class approach to treating these diseases and has the potential to reverse declines in cognitive, respiratory, and motor function. Tazbentetol is being evaluated as an investigational therapeutic in three disease indications: Alzheimer’s disease (NCT06427668), ALS (NCT05882695) and Schizophrenia (NCT06442462).

Current treatments for neurodegenerative, neuropsychiatric and neurodevelopmental conditions primarily focus on slowing disease progression or minimizing symptoms, leaving many without hope for improvement. Spinogenix is aiming to transform the treatment of these conditions through its pioneering first-in-class and paradigm-shifting synaptic regenerative and synaptic corrective therapeutics designed to restore depleted synapses and reverse synaptic degeneration and dysfunction.

Spinogenix is developing two novel therapeutics: Tazbentetol (formerly SPG302), which is designed to trigger neurons to produce new glutamatergic synapses and restore cognitive, motor, and other functions in ALS, Alzheimer’s disease, schizophrenia and other diseases; and SPG601, which is designed to work at the synaptic level to correct specific dysfunctions in Fragile X Syndrome (FXS) that underlie many core symptoms. The company has received FDA Orphan Drug and EMA designations for ALS as well as FDA Orphan Drug and Fast Track designations for FXS. More information on Spinogenix can be found at www.spinogenix.com or follow us on LinkedIn.