Spinogenix reports tazbentetol study demonstrated ‘rapid, sustained cognitive improvement’ in Alzheimer’s patients.
US biopharma Spinogenix today reported positive results from the completed Phase 2a study of its lead compound, tazbentetol, in the treatment of patients with Alzheimer’s disease, demonstrating “early and continued improvement” in multiple measures of cognition. The Los Angeles-based company is advancing an approach to neurodegenerative disease that centers on rebuilding the synaptic connections eroded by illness.
Spinogenix’s scientific rationale is built on the premise that restoring synaptic connectivity may allow for recovery of function rather than modest symptomatic relief or slowed decline. In Alzheimer’s disease, where synaptic deterioration emerges long before substantial neuron loss and tracks closely with cognitive decline, the company sees an opportunity to intervene at a point upstream from the mechanisms targeted by most treatments.
Tazbentetol, an investigational therapy formerly known as SPG302, is being developed as an oral treatment capable of restoring lost synapses and correcting synaptic dysfunction. The drug is one of a family of small molecules emerging from Spinogenix’s platform, which focuses on finding treatments designed to stimulate formation of new “glutamatergic synapses.” According to the company, these synapses, which rely on glutamate as a neurotransmitter, are among the earliest and most heavily affected in many neurodegenerative conditions.
The 24-patient trial, which met its primary endpoints, was run in Australia and evaluated once-daily dosing at 300 mg or 150 mg in people with mild-to-moderate Alzheimer’s disease,. According to findings presented at the recent CTAD conference, participants receiving the higher dose of the drug rapidly experienced a statistically significant mean gain of more than 2.5 points on the standardized mini mental status exam within four weeks. Improvement continued through 24-weeks across key cognitive and functional measures, and remained on an upward trajectory through 40 weeks.
“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 Spinogenix CEO Dr Stella Sarraf. “With our IND cleared in the US, we are looking forward to continuing global development of this first-in-class, and potentially transformative investigational treatment.”
Neurophysiological data, collected through EEG, provided evidence consistent with synaptic regeneration, including reversal of characteristic cortical slowing across several frequency bands. These changes align with the company’s preclinical work in Alzheimer’s mouse models, in which hippocampal synapse loss and memory performance improved within weeks of daily dosing.
“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,” said Professor Bruce Brew, neurologist and principal investigator at St. Vincent’s Hospital in Sydney, Australia.
Spinogenix is applying its regenerative model broadly across the so-called synaptopathies – a group of disorders marked by the loss or malfunction of synapses. Beyond Alzheimer’s, tazbentetol is also being evaluated in amyotrophic lateral sclerosis and schizophrenia. It has now completed Phase 2a trials in both ALS and Alzheimer’s, and the FDA has authorized an expanded access program for 200 people with ALS in the United States. A US-based Phase 2 study in schizophrenia is also underway.
