Cortexyme Inc.'s bacteria-targeting drug candidate, COR388, reduced levels of a protein associated with Alzheimer's disease risk in an early-stage trial, according to new data presented at the annual Clinical Trials on Alzheimer's Disease conference.

Cortexyme's stock was down by approximately 17.5% to $28.31 at market close Dec. 6, the day before the data presentation.

COR388, which zeroes in on the ApoE gene recently highlighted in Alzheimer's drug development by large pharma companies Biogen Inc. and Novartis AG, was evaluated in a phase 1b trial that enrolled healthy volunteers and people with Alzheimer's. The drug, given twice daily at 50 milligrams for 28 days, decreased ApoE4 and ApoE3 fragments in six Alzheimer's patients, a statistically significant decline compared to the three Alzheimer's patients treated with placebo.

COR388 works by targeting enzymes known as gingipains, thus protecting ApoE proteins from fragmentation, Cortexyme said Dec. 7.

The ApoE gene is associated with a greater risk of developing Alzheimer's disease, particularly the ApoE4 variety; according to Biogen, the ApoE4 gene carriers account for approximately two-thirds of the total Alzheimer's patient population.

South San Francisco, Calif.-based Cortexyme said ApoE and gingipains, which derive from the bacteria P. gingivalis, may be linked. Gingipains from P. gingivalis have been found in 90% to 100% of Alzheimer's patients, according to Cortexyme Chief Medical Officer Michael Detke.

During the biotech's Dec. 7 presentation, Cortexyme also noted that gingipains have a preference for cleaving ApoE4, producing more ApoE fragments seen in patients' brains and cerebrospinal fluid. This, in turn, may lead to the better-known effects of Alzheimer's, including neurodegeneration, inflammation and buildup of proteins amyloid and tau. Cells uninfected with P. gingivalis, on the other hand, did not exhibit significant ApoE protein fragmentation.

COR388 is currently in a phase 2/3 trial called GAIN, which is evaluating patients with mild-to-moderate Alzheimer's disease. Results are expected in the fourth fiscal quarter of 2021, Cortexyme said.

Cortexyme is one out of a handful of drugmakers still actively developing therapies for Alzheimer's, a disease that still has no cure.