NIA beams $49M to Lighthouse for bacteria-related Alzheimer's disease trial

Lighthouse Pharmaceuticals’ plan to become a beacon of hope for Alzheimer’s disease patients has received almost $50 million in U.S. government support.

The grant of $49.2 million has been supplied by the National Institutes of Health’s National Institute on Aging, with the specific aim of funding an ongoing phase 2 study of Lighthouse’s brain-penetrant lysine-gingipain (Kgp) inhibitor, dubbed LHP588.

The San Francisco-based biotech is planning to recruit 300 patients with mild to moderate Alzheimer’s disease as well as a Porphyromonas gingivalis infection. P. gingivalis is a bacteria best known for its role in a type of gum disease called chronic periodontitis. However, it has also been “implicated in chronic systemic inflammation and cognitive decline,” Lighthouse explained in an Aug. 22 release.

The phase 2 trial kicked off in February at the Northwest Clinical Research Center in Bellevue, Washington, although the company plans to expand to additional sites.

LHP588 is a successor to Lighthouse’s first-generation Kgp inhibitor atuzaginstat, which the biotech said had been linked to a 57% reduction in cognitive decline over 48 weeks in a phase 2/3 study of mild to moderate dementia patients with P. gingivalis infections.

"We are honored to receive this support from the NIA,” Lighthouse CEO Casey Lynch said in the release. “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.”

“We are proud to lead this pioneering trial aimed at modifying the disease process by targeting a known microbial driver of neuroinflammation and neurodegeneration,” Lynch added.

The latest advances in the Alzheimer’s space, such as Eisai and Biogen’s FDA-approved Leqembi, have come in the form of monoclonal antibodies that target the removal of amyloid-beta plaque buildup. But targeting bacteria to treat the neurodegenerative condition isn’t as strange as it sounds, with research in recent years suggesting bacterial viruses could play a role in a wide range of diseases.

“This grant enables a rigorous clinical test of a truly novel mechanism of action in Alzheimer's disease,” Marwan Sabbagh, M.D., chair of Lighthouse's clinical advisory board, said in this morning’s release. “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.”