Background
SPG302 is a small molecule compound developed by Spinogenix, a biotechnology company based in Los Angeles, California. SPG302 is believed to act on a regulator of the cytoskeleton, with the goal of increasing dendritic spine density and, in turn, improving cognitive and motor function (Trujillo-Estrada et al., 2021). SPG302 is currently in clinical trials for ALS/MND, Alzheimer’s disease (AD) and schizophrenia.
Some preclinical work has investigated the effects of SPG302 in models of Alzheimer’s disease and spinal cord injury. In a transgenic mouse model of Alzheimer’s disease, SPG302 was seen to mildly restore synaptic density in the hippocampus and improve cognitive function in hippocampal based tasks. Increased expression of postsynaptic proteins and synaptic density was observed (Trujillo-Estrada et al., 2021). In rats subjected to spinal cord injury, SPG302 marginally sped the recovery of diaphragm muscle activity (Fogarty et al., 2023).
Trial Design & Results
A first in human, phase 1/2a randomised, double-blind and placebo controlled study was started in July 2023 across 4 sites in Australia (Clinicaltrials.gov ID: NCT05882695). The study was composed of 3 parts:
- Part 1 – a single ascending dose (SAD) study in healthy volunteers, who were randomised 3:1 SPG302 to placebo
- Part 2 – a multiple ascending dose (MAD) study in healthy volunteers who were randomised 3:1 SPG302 to placebo and received a daily dose over 5 days, with a follow up safety visit on day 12 (±3 days)
- Part 3 – people living with ALS/MND were randomised 3:1 SPG302 to placebo. They were given a daily dose for 28 days, with a safety visit conducted 30 days (±7 days) after the final dose.
The primary outcome measure of all parts of the study was to assess incidence, nature, and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs). Secondary outcomes in healthy volunteers included SP302 plasma concentrations and the effect of food on the pharmacokinetics of the compound. Secondary outcomes for participants with ALS also included clinical measures such as spirometry and the Amyotrophic Lateral Sclerosis Functional Rating Scale-revised (ALSFRS-R). Participants living with ALS/MND from the phase I study were given the opportunity to take part in an open label extension to investigate the long-term safety, tolerability, and efficacy of SPG302 administered orally (Clinicaltrials.gov ID: NCT06903286). A total of 16 people living with ALS/MND will continue with the dose they received at the end of the first trial and will self-administer SPG302 orally for up to 52 weeks; they will have an in-person clinic visit every 3 months (± 3 days) and a monthly phone call.
Some of the results from the top line results from the Phase 2 program were presented at the Northeast Amyotrophic Lateral Sclerosis Consortium (NEALS) Annual Meeting in October 2025. The company communicated through a press release that SPG302 is safe and well tolerated in the studied cohort over 6 months at an oral dose of 300 mg daily, with some suggested clinical benefits. However, no data is publicly available yet to corroborate this statement. Some additional data was presented at the MNDA Symposium on December 5th, 2025, suggesting mild effect in slow progressors according to exploratory measures. The trial was relatively small, so these findings should be interpreted with caution and will need to be confirmed in larger studies.
SPG302 was granted orphan drug designation for the treatment of ALS/MND in both the US and European Union. In May 2025, the Food and Drug Administration (FDA, US) gave authorization for an Expanded Access Cost Recovery Program (EACRP) for 200 people living with ALS/MND who meet eligibility criteria in the US (Clinicaltrials.gov ID: NCT07088159). An EACRP allows sponsors to recover the direct costs of providing access to a therapy, without making a profit. As a result, people living with the disease are likely required to pay for access to the program.
SPG302 is also being studied in two phase II clinical trials for Alzheimer’s disease (in Australia; Clinicaltrials.gov ID: NCT06427668) and schizophrenia (in the US and Australia; Clinicaltrials.gov ID: NCT06442462).
Summary
SPG302 is a synthetic small molecule compound produced by Spinogenix, which targets defective synapses. A randomised, double blind, placebo-controlled study was carried out to assess safety and tolerability of SPG302 in healthy volunteers and people living with ALS/MND. No results are publicly available for this study yet. Participants with ALS/MND have been given the opportunity to take part in an open label extension for up to 52 weeks to evaluate long term safety and tolerability of SPG302.
International Alliance of ALS/MND Associations
April 2026
Disclaimer: Consult with a healthcare professional to determine if you could potentially participate in a SPG302 clinical trial. Always disclose your medical history, including any drugs, natural supplements, or herbal medicines currently being used.
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