Kancera’s Unique Approach to COVID-19: Attack the Fractalkine System


Thomas Olin, chief executive officer of Kancera, took time to discuss the company, the Fracktalkine pathway and the upcoming clinical trial.

Because a major feature of COVID-19 infections is the cytokine storm, numerous biopharma companies are testing drugs that control the immune system’s hyper-response in the disease. Fractalkine is the only known member of the CX3C chemokine family. It is a cytokine protein implicated in numerous areas of hyper-inflammation including, potentially, COVID-19.

Stockholm, Sweden-based biotech company Kancera AB recently received approval from the Swedish Medical Products Agency to initiate a clinical trial of KAND567, which blocks the Fractalkine receptor that plays a major role in triggering the body’s inflammatory process. Thomas Olin, chief executive officer of Kancera, took time to discuss the company, the Fracktalkine pathway and the upcoming clinical trial.

Kancera is located in the Karolinska Science Park in Stockholm and its key staff have a background with AstraZeneca, Pharmacia and the Karolinska Institute. The focus of the company for the last five years has been on cancer and immunomodulation, said Olin, and its most advanced projects are KAND567 and KAND145, focused on targeting hyperinflammation by blocking the Fractalkine system.

The Fractalkine receptor is expressed on monocytes and macrophages, natural killer (NK) cells and T-cells.

“The ligand fractalkine is expressed in a membrane bound form on endothelial cells and a soluble form,” Olin said. “The membrane-found form acts as an adhesion molecule and the soluble as a chemo-attractant. Together, this ligand/receptor of the fractalkine system regulates attraction and infiltration of immune cell into tissues triggering inflammation and repair.”

Olin noted that historically, the fractalkine system was thought to be primarily involved in resolution of inflammation and repair. But recent research suggests that the “fractalkine system drives both chronic and acute inflammatory disease in people and, potentially, blocking the system can cause remission in hard-to-treat autoimmune disease.”

It has now been shown that the fractalkine system triggers hyperinflammation after acute tissue damage and severe viral infection.

The upcoming Phase II clinical trial is expected to begin in the third quarter of this year with results in the fourth quarter 2020 and first quarter 2021.

The trial will study 40 patients, half treated with KAND5467 and the other a placebo. KAND567 is an oral medication taken via capsule twice a day for seven days. Follow-up health checks will be performed after completion and 90 days later.

Olin said KAND567 has an advantage over some of the antibody approaches because it is a small molecule, which can reach “damaged areas characterized by flow and exposure is easier to modulate short term, which could be the key to balancing processes that drive inflammation and repair.”

The study followed results from the Phase Ib program, which was conducted in Finland. In early March, the company presented positive data from that trial in the form of good tolerability and a favorable safety profile after intravenous treatment. The early work on KAND567 was intended for acute myocardial infarction.

This data supported the drug’s safety profile and also demonstrated that the drug’s activity could decrease the infiltration of monocytes carrying the fractalkine receptor into the vasculature. And those high fractalkine levels, Olin said, are markers of poor prognosis. It is the circulating monocytes that are likely the cause of that poor prognosis because they express high levels of fractalkine receptors and are attracted to regions of inflammation caused by the release of CX3CL1, a soluble fractalkine ligand.

In non-COVID-19 patients in the clinic, elevated fractalkine levels have been noted in acute respiratory distress syndrome (ARDS) and in sepsis.

As a result of the ongoing COVID-19 pandemic, the company decided in May to focus its development of KAND567 on infectious diseases. Part of that process was to cut staff in its preclinical research areas, which would decrease the company’s cost base by about SEK 8 million a year (Slightly under $1 million U.S.). It also is focused on taking KAND145, its preclinical drug candidate, into the clinic.

“In early May, we announced a patent application for KAND567 and KAND145 for the treatment and prevention of hyperinflammation in viral infections, and shortly thereafter we submitted an application to the Swedish Medicines Agency to conduct a Phase II clinical study documenting the potentially protective effect of the drug candidate KAND567 in patients with COVID-19,” Olin said in an earlier statement. “The study is intended to be conducted in collaboration with Capio St. Görans Hospitals and the Science for Life Laboratory (SciLifeLab). By opening up this new area of use for fractalkine inhibitors, we hope to contribute to the treatment of severe viral infections caused by COVID-19 and other viruses that cause the same type of hyperinflammation.”

The Phase II trial will be at one clinical site, Capio St. Görans Hospital and led by clinical investigators Mantas Okas and Mats Wistrand. The center had treated more than 4,000 COVID-19 patients as of the end of May. Peter Brodin, with the SciLifeLab and Karolinska Institute will perform analysis of the patients’ genetic and immunological profile during the trial.

The focus will be on COVID-19 patients with hypoxia who have not cleared the initial infection and are either in the earlier stages of the hyperinflammatory response or at risk of developing it. They will be able to define that patient group on the basis of several factors, including the C-reactive protein (CRP) level, and by oxygen saturation. Patients with less than 94% oxygen saturation or who require one to six liters of supplemental oxygen per minute in order to maintain oxygen saturation levels between 93% and 96% will be eligible for the trial.

KAND-567 was originally developed by AstraZeneca for multiple sclerosis. Kancera picked it up while still in preclinical studies and planned it for immuno-oncology indications. Then, a trial with UK clinical collaborators suggested fractalkine was involved in the hyperinflammation that comes after percutaneous coronary intervention, or coronary angioplasty after a myocardial infarction. That trial is still on the table but planned for some time in 2021.

In addition to the coronary study, Olin said the drugs have applications for “spinal cord injury: diminishing neural cell death in the acute phase of the injury and thereby preserving mobility” and “autoimmune diseases, e.g. Cohn’s: Eisai have published data showing complete remission in hard to treat patients following treatment with fractalkine targeted antibody.”

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