By: IPP Bureau
Last updated : August 28, 2025 10:35 am
LHP588 is an oral, brain-penetrant lysine-gingipain (Kgp) inhibitor designed to block the key virulence factor of P. gingivalis
Lighthouse Pharmaceuticals, a clinical-stage biopharmaceutical company developing precision therapies for neurodegenerative diseases, announced it has received a $49.2 million grant from the National Institute on Aging (NIA), part of the NIH, to support a Phase 2 clinical trial of LHP588 in Alzheimer’s disease (AD) patients with confirmed Porphyromonas gingivalis (P. gingivalis) infection.
LHP588 is an oral, brain-penetrant lysine-gingipain (Kgp) inhibitor designed to block the key virulence factor of P. gingivalis, reducing its toxicity and viability. Previous studies of a Kgp inhibitor in mild to moderate AD showed significant slowing of cognitive decline in P. gingivalis-positive patients, with reductions in salivary P. gingivalis correlating to improved clinical outcomes.
The Phase 2 SPRING trial will enroll 300 patients with mild to moderate AD and P. gingivalis detected via saliva test. Participants will be randomized to receive a high or low dose of LHP588, or placebo, in a double-blind, placebo-controlled design to evaluate safety, tolerability, and efficacy.
"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, CEO 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 more than 6 million Americans and has no cure. Research suggests chronic infection with P. gingivalis contributes to AD progression through gingipains—neurotoxic proteases that promote inflammation, neuronal damage, amyloid-beta buildup, and tau pathology.
"This grant enables a rigorous clinical test of a truly novel mechanism of action in Alzheimer’s disease," said Marwan Sabbagh, M.D., 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."