Lighthouse Pharmaceuticals, a US-based clinical-stage biopharmaceutical company, announced on Thursday that it has received approval from the US Food and Drug Administration (FDA) for the Investigational New Drug (IND) application of LHP588, the company's next-generation gingipain inhibitor, for the treatment of P gingivalis-positive Alzheimer's disease.

The company received the 'Study May Proceed' letter from the FDA based on review of the comprehensive IND package, which includes safety, chronic toxicology, manufacturing, Phase one human data, and the proposed Phase two SPRING (Stopping PRogression of P. gINGivalis-positive Alzheimer's disease) trial protocol.

LHP588 is a next-generation, brain penetrant small-molecule gingipain inhibitor that demonstrated safety and tolerability in the completed Phase one study, along with plasma levels sufficient to engage the target with just once-daily oral dosing.

The Phase 2 SPRING clinical trial, a randomised, double-blind, placebo-controlled study, is intended to evaluate the efficacy and safety of once-a-day dosing of LHP588 for the treatment of P. gingivalis-positive mild to moderate Alzheimer's disease. Around 300 subjects will be enrolled in the trial and randomised into three arms (placebo, 25mg and 50mg) for 48 weeks of treatment. Subjects must have mild to moderate Alzheimer's disease and evidence of P. gingivalis infection, based on a saliva test. The GAIN trial of the first-generation gingipain inhibitor, atuzaginstat, demonstrated that subjects with mild to moderate AD and a positive P gingivalis saliva test had a dose-dependent, 57% indicating cognitive decline on the prespecified proof of efficacy endpoint, ADAS-Cog11, compared to the placebo group (p = 0.02).