Preliminary Phase 2 Data Support Therapeutic Development of Synaptic Regenerative Drug SPG302 in ALS

Topline data from a completed phase 2a trial (NCT05882695) highlighted the therapeutic benefits of SPG302, a synaptic regenerative drug, to treat patients with amyotrophic lateral sclerosis (ALS). All told, treatment with the investigational, once-a-day pill led to significant slowing of disease progression along with improvements in ALS-associated patterns on EEG, further supporting its development as a first-in-class approach.^1,2

Presented as a poster at the recently concluded Northeast Amyotrophic Lateral Sclerosis Consortium (NEALS) Annual Meeting, the analysis comprised patients with ALS who received either SPG302 (n = 18) or placebo (n = 5) for a 28-day period, followed by an open-label extension lasting 140 days. Coming into the trial, most patients were on riluzole (n = 19; 82.6%), with few also on edaravone as well (n = 2; 8.7%).

In terms of efficacy, preliminary data showed that 82% of SPG302-treated patients demonstrated stable or improved rate of disease progression at the end of treatment, as assessed through the ALS Functional Rating Scale-Revised (ALSFRS-R). When compared with historical controls from the PRO-ACT database (n = 299), patients on the investigational drug exhibited a 76% slower rate of decline through 6 months.

"We are very encouraged with the positive Phase 2a trial results for SPG302, in our initial proof of concept ALS study, demonstrating the potential of this new regenerative therapy," Stella Sarraf, PhD, chief executive officer and founder at Spingogenix, said in a statement.¹ "As we plan our larger registrational directed ALS trial, we also remain committed to making this investigation therapy available to patients who do not qualify for clinical trials through our FDA-cleared Expanded Access Program."

At oral daily doses of 300 mg, SPG302 was considered safe during the 6-month period, with no observed treatment-related serious adverse events (AEs). Treatment-emergent AEs were found in 16.7% (4 of 24) of treated patients, 3 of which were related to elevated liver enzymes. Serious AEs, such as pulmonary embolism, pneumonia aspiration, respiratory failure, vomiting, and joint injury, were observed, but were unrelated to the study drug.

READ MORE: FDA Issues Complete Response Letter for Spinocerebellar Ataxia Agent Troriluzole

On EEG recordings, investigators observed improvements in ALS-associated patterns, further adding to SPG302’s efficacy profile. During the double-blind period, SPG302 was shown to normalize brain EEG power across delta and gamma frequencies, which remained consistent through weeks 8 and 24. In addition, there were observed treatment effects in whole brain and specifically in motor cortex.

"there is a need to develop new therapies that target neuronal repair pathways for people with ALS. SPG302 represents an important new approach to target synapse loss in ALS," Merit Cudkowicz, MD, MSc, inaugural executive director of the Mass General Brigham Neuroscience Institute, said in a statement.¹ “I look forward to the next phase of drug development to assess the potential of SPG302 and I am grateful to the leadership at Spinogenix for their additional commitment of a parallel expanded access program for people not eligible for their planned clinical efficacy trials."

For patients who were unable to receive the drug in the double-blind period, the company is providing access to 200 patients with ALS through an expanded access program. Separate from ALS, SPG302 remains in clinical trials for other conditions like Alzheimer disease (AD; NCT06427668) and schizophrenia (NCT06442462). Earlier this year, at the 2025 Alzheimer’s Association International Conference, the company presented preliminary findings from the phase 2 study, with SPG302 showing a favorable safety profile.

The initial cohort of the phase 2 trial randomly assigned 12 patients with early-stage AD to receive 300 mg SPG302 or placebo as an oral tablet for a 4-week treatment period, followed by a 24-week extension. Investigators assessed outcomes on a monthly basis, including standard cognitive assessments, quantitative neurophysiological measures sensitive to synaptic density, quality of life and activities of daily living measures, and other measures. Overall, the results showed improvements in Mini-Mental State Examination among most patients, with corresponding changes in other cognitive measures.

During the meeting, NeurologyLive^® caught up with coauthor Sharron Gargosky, PhD, chief development officer at Spinogenix, to discuss the data and the significance of the early findings. In the clip below, Gargosky broke down the efficacy and safety outcomes, and how they support SPG302 both as a monotherapy and as an adjunctive therapy to standard of care in AD.

REFERENCES
1. Spinogenix Presents Topline Phase 2a Clinical Trial Results for SPG302, a First-in-Class ALS Treatment. News release. Spinogenix. November 4, 2025. Accessed November 4, 2025. https://www.prnewswire.com/news-releases/spinogenix-presents-topline-phase-2a-clinical-trial-results-for-spg302-a-first-in-class-als-treatment-302603975.html
2. Rowe D, Henderson R, Shultz D, et al. Phase 2a Topline Clinical Results Evaluating Neurophysiological and Functional Measures in SPG302-treated ALS Participants. Presented at: 2025 NEALS Annual Meeting.
3. Priest L, Cayzer A, Brew B, et al. Early positive signals of cognitive outcomes in mild to moderate Alzheimer patients treated with the synaptic regenerative small molecule, SPG302. Presented at: 2025 Alzheimer’s Association International Conference; July 27-31; Toronto, Canada. Abstract 109023.