Assessing Phase 2 Data of Tazbentetol in Alzheimer Disease: Bruce Brew, MD, DSc, FRACP, FAAN

WATCH TIME: 4 minutes | Captions are auto-generated and may contain errors.

"At week 4, we found that the Mini-Mental State Exam score improved by around 2.5-plus points. So that’s quite dramatic. I can’t think of really any other intervention that’s comparable at such a rapid, early time point."

Tazbentetol (Spinogenix), formally known as SPG302, is a novel synaptogenic small molecule currently being assessed in a randomized, double-blind, placebo-controlled phase 2 study (NCT06427668) of patients with mild-to-moderate Alzheimer disease (AD) in Australia.¹ In the trial, participants (n = 24) were enrolled into 1 of 2 cohorts and randomized 2:1 to placebo or to active intervention at 300-mg or 150-mg doses for up to 24 weeks, starting with a 4-week placebo-controlled period. Patients in the study were eligible to continue treatment beyond the open-label period for an additional 52 weeks at a 300-mg dose of tazbentetol.

Led by neurologist Bruce Brew, MD, DSc, FRACP, FAAN, the primary end points of the trial included Mini-Mental State Exam (MMSE), Clinic Dementia Rating Scale – Sum of Boxes (CDR-SB), Activities of Daily Living (ADL) and neurophysiological EEG biomarker measures of AD-related brain activity. Topline results of both cohorts from the phase 2 study, presented at the recently concluded 18th Clinical Trials on Alzheimer’s Disease (CTAD) Conference, held December 1-4, 2025, in San Diego, California, showed that tazbentetol demonstrated early signs of improvement across multiple key end points and was safe in patients with mild-to-moderate AD.²

Following the 2025 CTAD Conference, NeurologyLive^® spoke with Brew, who serves as the director of the Peter Duncan Neurosciences Unit at St Vincent's Hospital in Sydney, Australia, about the recently presented topline phase 2 results. In the conversation, he outlined improvements observed in cognitive assessments at 4 weeks in the study, while also noted that no changes were reported in traditional AD biomarkers, which he said was consistent with the proposed mechanism of action. In the open-label phase, he added that additional cognitive measures continued to show positive changes, and the therapy demonstrated an acceptable safety profile overall.

Click here to view more coverage of CTAD 2025.

REFERENCES
1. Brew B, Priest L, Cazyer A, et al. Completion of a Phase 2 Trial Evaluating Safety and Efficacy of the Synaptic Regenerative Small Molecule SPG302 in Participants With Mild-to-Moderate Alzheimer’s Disease. Presented at: CTAD 2025; December 1-4; San Diego, CA. OC31.
2. Spinogenix Reports Evidence of Rapid, Sustained Cognitive Improvement in Alzheimer’s Patients from Phase 2a Trial of TAZBENTETOL (formerly SPG302). News release. Spinogenix. December 8, 2025. Accessed January 5, 2025. https://www.spinogenix.com/spinogenix-reports-evidence-of-rapid-sustained-cognitiveimprovement-in-alzheimers-patients-from-phase-2a-trial-of/