The trial, which began in October 2020, is a placebo-controlled double blind trial involving 40 COVID-19 patients at Capio St. Göran’s Hospital in Sweden, and deep-profiling of the immune system at SciLifeLab, Karolinska Institute. A further phase 2 clinical trial, planned for the UK in early 2021 will involve heart attack patients.
KAND567 has been developed to tune the immune system to preserve organ function and promote rehabilitation after COVID-19 or heart attack.
“Hyperinflammation, brought on by an immune system under pressure, is a leading cause of COVID-19-related respiratory failure, as well as cardiovascular failure,” said Thomas Olin, CEO of KanceraArray. “When patients with attacks in primary centers go through the number one after percutaneous coronary intervention (PCI), reperfusion triggers hyperinflammation that, as with COVID-19, increases the risks of severe headaches and organ failure. After a heart attack, about 25% will suffer some other serious heart complication or die within five years, partly due to hyperinflammation.
KAND567 is a small molecule treatment which blocks the fractalkine receptor involved when the immune system starts an exaggerated inflammatory response. This prevents damaging immune cells infiltrating vital organs (Fig. 1).
Fig. 1 | KAND567 is an allosteric antagonist of CX3CR1. KAND567 selectively blocks the fractalkine axis and therefore infiltration of immune cells into tissue.
“Among the dominant cytotoxic cells identified in COVID-19 patients, cells known to be regulated by the fractalkine system (CX3CR1/L1) are prominent. Blood concentration of the ligand fractalkine, which acts as a chemo-attractant of immune cells into tissue, is shown to increase significantly with severe COVID-19,” Olin said.
“Corticosteroids, recommended for severe cases of COVID-19, suppress T cells and B cells and likely prevent an effective immune reaction against the virus,” Olin said. “Our knowledge so far shows that, even if KAND567 exerts the desired effect, an effective immune reaction against foreign structures such as viruses is maintained. ” Preclinical insights also show that KAND567 would possibly be effective in blocking hyperinflammation in other settings, including chemotherapy, autoimmune diseases, pancreatitis, and spinal cord injury.
Older patients with COVID-19 are more likely to develop respiratory failure and cardiovascular failure. An older immune formula is characterized by the depletion of the motifs needed to fight infection, while other immune motile populations become markedly pro-inflammatory. the risk of hyperinflammation in older people, but also in younger people whose immune systems are under pressure and age prematurely.
The purpose of the COVID-19 test KAND567 is to block cytotoxic immune cells at an early or intermediate stage before they infiltrate important organs. About 25% of intensive care patients with COVID-19 die. Lives may be stored if patients do not move from the initial lung infection to comprehensive care. Among patients who transmit the virus, a significant proportion suffer long-term complications. “The symptoms are quite similar to those of an autoimmune disease with a relapsing-remitting tendency adding neurological and cardiovascular symptoms. So if we can block the dynamics of this type of immune response, we hope that rehabilitation will advance in the long term,” Olin said.
While the existing trial consists of a 7-day remedy intended to treat the critical phase of hyperinflammation development, in the longer term, KAND567 can be used only in the relapse phase as an intermittent remedy to treat relapses.
Around part a million patients year in the EU and USA go through PPCI following a primary center attack in the anterior center wall. Treatment aims to open the blocked vessel, lessen the death of center tissue and in all probability save lives.
However cardiac damage caused by hyperinflammation, which appears after reperfusion with PPCI is, according to current research, one of the main factors why approximately 25% of patients suffer another severe cardiac complication or die within 5 years despite best standard of care.
A study of more than 1,300 heart attack patients showed activation of the immune system, i. e. , the fractalkine system, within minutes of PPCI, which is strongly correlated with an increased risk of premature death three years later (hazard ratio: 2 ,4). that protects against inflammatory damage caused by reperfusion,” Olin said. “KAND567 is well positioned to be the first in its class to do so. “
Two successful clinical trials for the drug would lead to requests for rapid regulatory procedures in the EU and US. U. S.