NOVATO, Calif., July 13, 2026 /PRNewswire/ — Lighthouse Pharmaceuticals today announced new analyses from the Phase 2/3 GAIN trial demonstrating that atuzaginstat, a gingipain inhibitor targeting Porphyromonas gingivalis (Pg), was associated with benefits in several neuropsychiatric symptoms, including agitation and aggression, among Pg-positive patients with mild-to-moderate Alzheimer’s disease.
The findings, being presented at the Alzheimer’s Association International Conference (AAIC) 2026, build on previously reported results showing that atuzaginstat slowed cognitive decline by 57% (p=0.02) on the ADAS-Cog11 in a prespecified subgroup of Pg-positive patients.
New analyses of Neuropsychiatric Inventory (NPI) subdomain data showed significant benefits in agitation/aggression, disinhibition, elation/euphoria, and apathy after 48 weeks of treatment compared with placebo. These benefits were accompanied by significant reductions in caregiver distress, suggesting meaningful improvements for both patients and their families. In Pg-negative patients, no significant benefit was observed in reduction of neuropsychiatric symptoms or caregiver distress.
“Agitation and other behavioral symptoms are among the most challenging aspects of Alzheimer’s disease for patients and caregivers, yet no disease modifying treatments exist,” said Michael Detke, MD, PhD, Chief Medical Officer of Lighthouse Pharmaceuticals. “These findings suggest that targeting gingipains may provide benefits beyond cognition in Pg-positive Alzheimer’s disease, in reducing and preventing emergence of neuropsychiatric symptoms.”
Lighthouse is currently advancing LHP588, a next-generation gingipain inhibitor with once-daily dosing and favorable Phase 1 safety results. The ongoing Phase 2 SPRING trial is evaluating LHP588 in approximately 300 Pg-positive Alzheimer’s patients and includes assessments of agitation, aggression, cognition, and function.
The SPRING trial is currently enrolling participants across the United States. Additional information and site locations are available at www.springclinicaltrial.com.
Poster Presentation
The data will be presented at the AAIC during the poster session on Monday, July 13, 2026 in the exhibit hall from 730 a.m. – 430 p.m (Abstract #12934). The poster will also be available at https://www.lighthousepharma.com/publications following the presentation.
About Lighthouse Pharma
Lighthouse Pharmaceuticals is a clinical-stage biopharmaceutical company developing novel small-molecule therapeutics for chronic neurodegenerative and inflammatory diseases, with lead asset LHP588 being evaluated in the NIH-funded SPRING trial for Alzheimer’s disease. For more information, visit www.lighthousepharma.com.
The SPRING trial is supported by the National Institute on Aging of the National Institutes of Health under Award Number R01AG088524. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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