Background

SNP318 inhibits the enzyme lipoprotein-associated phospholipase A2 (Lp-PLA2). Also known as plasma platelet-activating factor acetyl hydrolase, this enzyme produces inflammatory mediators that damage blood vessels and increase the permeability of the blood-brain barrier. Lp-PLA2 circulates in the blood in association with LDL cholesterol, and is linked to the formation of atherosclerotic plaques. Inhibitors were originally developed to treat atherosclerosis; the rationale for use in Alzheimer’s disease stems from their anti-inflammatory, anti-oxidative, and pro-vascular effects.

SNP318 is a second-generation Lp-PLA2 inhibitor related to rilapladib, a compound discovered at GlaxoSmithKline, and tested for AD. In a Phase 2 trial in people with both mild Alzheimer’s dementia and neurovascular disease, rilapladib improved a composite of executive function/working memory, but did not change CSF Aβ42 or other endpoints (Maher-Edwards et al., 2015).

In June 2022, SciNeuro bought the rights to rilapladib and other Lp-PLA2 inhibitors from GSK (press release). SciNeuro claims that SNP318 penetrates the CNS better than rilapladib (press release).

Findings

In March 2023, SNP318 began a Phase 1 safety, tolerability and pharmacokinetics study in 86 healthy adults. The placebo-controlled trial includes single ascending doses starting at 1 mg, and multiple doses starting at 30 mg, all in capsule form. It includes cerebrospinal fluid sampling. The study is running in Australia through October 2023. 

For details on SNP318 trials, see clinicaltrials.gov