New results from clinical trial shows continued progress for a drug to treat celiac disease

KAN-101 is well tolerated at increased dose levels, study presented at DDW shows

By Amy Ratner, director of scientific affairs

Increased doses of a drug being studied for the treatment of celiac disease tempered the response to gluten in celiac disease patients and remained as safe and well tolerated as lower doses, according to results presented at Digestive Disease Week (DDW).

KAN-101 modulated cytokine responses after a gluten challenge given to study participants, indicating the development of tolerance by the immune system and regulation of immune response, the study says. The drug is being investigated by Anokion, a clinical-stage biotechnology company focused on treating autoimmune disease by restoring normal immune tolerance.

Body’s disease fighting soldiers

Cytokines are small, secreted proteins released by cells that have a specific effect on the interactions and communications between cells. When someone has celiac disease, their immune system incorrectly reads gluten proteins as invaders. This miscue triggers T-cells, which function as the body’s disease fighting soldiers, to release cytokines and attack. This attack causes inflammation and tissue destruction.

KAN-101 is focused on restoring normal immune tolerance of gluten by targeting specific receptors on the liver, setting off a cascade of events that re-teach the immune system not to respond to gluten. Unlike broad immunosuppressants, KAN-101 targets only the part of the immune system that drives celiac disease.

This is the third year Anokion has presented study results at DDW as Kan-101 moves through various stages of clinical trials. The company concluded its earlier Phase 1 ACeD trial and is now simultaneously conducting Phase 1/b ACeD-it and Phase 2 SynCeD clinical trials.

In Phase 1, the safety of a drug is investigated in a small group of study participants, while in Phase 2 the investigation into safety continues and the effectiveness of the drug and the way it works in the body is also evaluated in a larger group of study participants.

Several other companies working on drugs to treat celiac disease also presented results at DDW.

How Kan-101 is designed to work

The drug is designed to deliver proteins in an immune tolerance pathway in the liver, leveraging the natural process routinely performed in the liver. One of the liver’s functions is to clear dying cells without causing inflammation. Lower doses of the drug were tested in an earlier phase of clinical trials.

In results of the phase of the ACeD-it trial presented at DDW, celiac disease patients were given one of two dose amounts through an IV on three different days. Fifteen days after the last dose, they had a one-day gluten challenge. Blood plasma samples were taken at various times for analysis, including evaluation of Interlukin-2 (IL-2) response following the gluten challenge. IL-2, a biomarker or red flag for celiac disease activity, is a cytokine signaling molecule in the immune system. Previous research has shown a correlation between IL-2 and symptoms in celiac disease patients, including nausea and vomiting.

Six patients were originally enrolled in the study, but one withdrew after the first IV dose of the drug and another completed treatment but developed COVID-19 prior to the gluten challenge. All study participants reported at least one treatment adverse effect, all of which were either mild or moderate in severity. Most were consistent with symptoms that those with celiac disease experience when they eat gluten. No serious adverse effects were reported. Kan 101 did not accumulate in the body with repeat doses, the study says.

Phase 2

In a portion of patients treated with the drug, “the broader cytokine response to the [gluten challenge] was modulated and associated with lack of nausea,” according to the study. This was consistent with results of an earlier phase of clinical trial.

The findings from this phase of study will allow additional dose amounts to be used in the Phase 2 investigations of the drug, the authors conclude.

“We remain excited by KAN-101’s ability to reduce the broader inflammatory mechanisms triggered by gluten exposure and its potential to offer durable treatment options to patients where there is currently no disease-modifying therapy available,” Deborah Geraghty, Ph.D., chief executive officer of Anokion, said in a press release following the presentation at DDW. DDW is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery.