Preclinical findings from Kancera

The company has announced the first public presentation of data for KAND567, its fractalkine receptor antagonist, in preclinical models of cardiovascular disease and its predicted translation to humans.
The findings was announced at the European Society of Cardiology (ESC) Congress 2019 in Paris, France. The company’s oral presentation entitled “KAND567, the first selective small molecule CX3CR1 antagonist in clinical development, mediates anti-inflammatory cardioprotective effects in rodent models of atherosclerosis and myocardial infarction” was given by co-author Ioakim (Kim) Spyridopoulos, a professor of cardiovascular gerontology at Newcastle University and director of the university’s Cardiovascular Research Centre. Co-authors on the scientific work include researchers at Newcastle University, Karolinska Institute, AstraZeneca plc and Kancera.
About KAND567 and the fractalkine system
Kancera has KAND567 in clinical testing for myocardial infarction. The small molecule blocks signaling at the fractalkine receptor, also called CX3CR1, that drives immune cell responses at the infarction site during the minutes and hours after a heart attack. Blocking the action of these cells reduces the acute inflammation behind the cardiovascular damage that contributes to the risk of subsequent heart attacks and heart failure, as well as morbidity and poor quality of life, in these patients.
“The fractalkine system blocker KAND567 is expected mainly to act as a ‘first line of defense’ controlling the entrance of these intruder cells, rather than eliminating them,” said Kancera CEO Thomas Olin. “Moreover, as inflammation in general can be both beneficial and a threat, healthcare and the industry are looking to develop new treatments that are more specific on both mechanisms and timing aspects.”
Other clinical studies in heart attack patients have demonstrated ischemia/reperfusion injury is associated with high levels of fractalkine signaling and low numbers of circulating immune cells expressing the fractalkine receptor. While the number of these cells return to normal about 24 hours after infarction, the transient drop in cell counts is a strong predictor of survival three and six years later.
If successful, Kancera’s program could change the paradigm of heart attack treatment by stopping the damaging inflammation before it starts.
Ongoing Phase Ib trial
Kancera has KAND567 in an ongoing Phase Ib trial in healthy subjects to study the safety and tolerability of the compound and to generate information on optimal infusion rate to quickly reach a specific desired plasma concentration. In June, Kancera announced positive interim results from the trial. Last week, the company announced development of a new dosing strategy for the trial that would combine intravenous and oral dosing of KAND567, in line with clinical practice for infarction patients, to improve tolerability. Kancera expects to report results from the Phase Ib trial in December and enter Phase II for myocardial infarction in the first half of 2020.
Kancera has KAND145, a second-generation fractalkine receptor antagonist, in development for inflammatory diseases.
Photo of Thomas Olin: Kancera
Published: September 4, 2019