COR588, New Gingipain Inhibitor, Safe to Take Once Daily

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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COR588, Quince Therapeutics’ investigational oral small molecule for mild to moderate Alzheimer’s disease, appears to be safe and well tolerated, according to results from a Phase 1 trial, the company announced. (The company was known as Cortexyme until Aug. 1.)

The recently completed single and multiple ascending dose clinical trial (NCT04920903) tested how safe and well tolerated COR588 was versus a placebo when taken by mouth once daily for up to 10 days in 64 healthy adults.

COR588 is designed to inhibit the activity of gingipains, a type of toxic protein made by the bacteria Porphyromonas gingivalis (P. gingivalis). This bacteria is best known for causing gum disease and has also been linked to Alzheimer’s development.

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Both the bacteria and its toxins can be found in the brain of patients with Alzheimer’s, where they are thought to trigger inflammation around nerve cells. As the nerve cells become damaged, Alzheimer’s symptoms may occur, such as memory loss and problems with thinking.

In an attempt to stop or slow further damage to nerve cells, Quince cast a series of gingipain inhibitors for the potential treatment of Alzheimer’s.

COR388, also known as atuzaginstat, was generally safe when taken as an oral capsule of either 40 or 80 mg twice daily for 48 weeks (almost a year), but a 643-patient Phase 2/3 clinical trial (NCT03823404), called GAIN, failed to meet its main goals within the 48 weeks of treatment. COR388 was not better than a placebo at slowing cognitive or daily functioning decline in the whole group of patients, yet it showed a trend toward slowing cognitive decline in those with more of P. gingivalis in their saliva.

Earlier this year, however, the U.S. Food and Drug Administration put a full hold on the COR388 clinical program for an undisclosed reason.

Now, the company is focusing its efforts on COR588, a second-generation small molecule that was selected based on a better safety margin than COR388 and improved pharmacokinetics — essentially how the body affects a medicine.

“COR588 was designed to be a potent and selective molecule with pharmacokinetics supportive of once daily oral dosing,” Michael Detke, MD, PhD, chief medical officer at Quince, said in a press release. 

The Phase 1 clinical trial included 64 healthy adults up to 55 years old who were randomly assigned to receive an oral capsule containing either COR588 or a placebo.

In the single ascending dose part of the study, which included 32 people, COR588 was well tolerated across a dose range from 25 to 200 mg. There were no serious side effects. Its half-life was 11 to 12 hours, meaning that its amount in the body is down by half after this time. This finding was consistent with a once-daily dosing.

In the multiple ascending dose study, COR588 was taken once daily for up to 10 days. The treatment was well tolerated across a dose range from 50 to 200 mg, with no serious side effects. COR588 was able to efficiently penetrate the central nervous system, an essential feature for medicines that are meant to act on the brain and spinal cord.

Within the next few days, the company will provide an update on the COR588 clinical program.