Groundbreaking Clinical Trial to Enroll 300 Patients in Double-Blind, Placebo-Controlled Study of Lysine-Gingipain Inhibitor

Lighthouse Pharmaceuticals, a clinical-stage biopharmaceutical company pioneering precision therapies for neurodegenerative diseases,  announced it has been awarded a $49.2 million grant from the National Institute on Aging (NIA), part of the National Institutes of Health (NIH), to support a Phase 2 clinical trial of LHP588 in Alzheimer's disease (AD) patients with a confirmed Porphyromonas gingivalis (P. gingivalis) infection. P. gingivalis is best known for its role as a keystone pathogen in chronic periodontitis and has been implicated in chronic systemic inflammation and cognitive decline.

LHP588 is an orally available, brain-penetrant lysine-gingipain (Kgp) inhibitor designed to selectively block the activity of this key virulence factor of P. gingivalis, thereby reducing the bacteria's toxicity and viability. A previous clinical study of a Kgp inhibitor in mild to moderate AD demonstrated significant slowing of cognitive decline in the prespecified P. gingivalis-positive subgroup and P. gingivalis reduction in saliva correlated significantly with improved clinical outcome measures.

The Phase 2 SPRING Trial will evaluate the safety, tolerability, and efficacy of a high and low dose of LHP588 compared to placebo in 300 patients with mild to moderate AD and a positive saliva test for P. gingivalis in a randomized, double-blind, placebo-controlled design.

"We are honored to receive this support from the NIA. It is powerful validation of the growing body of evidence connecting P. gingivalis to Alzheimer's disease and the potential of gingipain inhibition as a therapeutic strategy," said Casey Lynch, Chief Executive Officer of Lighthouse Pharma. "We are proud to lead this pioneering trial aimed at modifying the disease process by targeting a known microbial driver of neuroinflammation and neurodegeneration."

Alzheimer's disease affects over 6 million Americans and remains without a cure. Emerging evidence suggests that chronic infection with P. gingivalis contributes to the progression of Alzheimer's through the production of gingipains—neurotoxic proteases that promote inflammation, neuronal damage, amyloid-beta accumulation, and tau pathology.

"This grant enables a rigorous clinical test of a truly novel mechanism of action in Alzheimer's disease," said Marwan Sabbagh MD, Chair of Lighthouse Pharma's Clinical Advisory Board. "By directly inhibiting lysine-gingipain, LHP588 offers a targeted approach to intervening in the infectious and inflammatory cascade that may underlie the disease in P. gingivalis-positive AD patients."

SPRING will be supported by the NIA under award number R01AG088524. The content of this release is solely the responsibility of Lighthouse Pharma and does not necessarily represent the official view of the NIH.