Poolbeg expects first data for CRS drug in the summer
Jeremy Skillington, Poolbeg Pharma's chief executive.
Poolbeg Pharma is preparing to start a clinical trial of a drug that aims to block a life-threatening side effect of cancer immunotherapies, and hopes to have its first data in the summer.
The UK start-up has just had its first investigation site activated for the planned trial of lead drug POLB-001, which is being developed to prevent cytokine release syndrome (CRS), a reaction to immunotherapy that causes an uncontrolled cascade of inflammatory responses that attack the body and damage organs.
CRS first came to the fore when CAR-T cell therapies for blood cancers first emerged onto the market almost a decade ago, but it is also seen with drugs that attempt to redirect the immune system to attack cancers, particularly bispecific antibodies that encourage a T-cell response.
It can often be prevented using drugs like antihistamines and corticosteroids to blunt the inflammatory effect given before the immunotherapy is administered, although these are not always effective, while drugs like tocilizumab are used to block the inflammatory cascade if CRS breaks through. At the moment, there are no therapies specifically approved to prevent CRS.
Meanwhile, the risks are such that cancer immunotherapy patients need to be treated in specialised units where they can receive urgent care if needed – sometimes for a couple of weeks – which places a heavy financial burden on health systems and means patients sometimes have to travel long distances for treatment.
POLB-001, a small-molecule inhibitor of p38 mitogen-activated protein kinase (p38 MAPK) that has just been awarded a European patent, is designed to block a key signalling pathway that drives the production of cytokines and suppresses CRS.
To test the hypothesis, Poolbeg is running the TOPICAL clinical trial across six NHS hospitals involving 30 patients with the blood cancer multiple myeloma, who are scheduled for treatment with Johnson & Johnson's BCMAxCD3 bispecific antibody Tecvayli (teclistamab), to see if POLB-001 can reduce the risk of CRS.
As the reaction occurs within a few days or weeks of immunotherapy for the cancer, the company hopes to get a result from the study very quickly.
"We believe POLB 001 has the potential to transform the cancer immunotherapy field through the prevention of CRS. This could not only improve patient quality of life, but also expand the number of patients that can receive these life-saving cancer immunotherapies," said Jeremy Skillington, Poolbeg's chief executive.
The company has previously estimated that POLB-001 could address a potential $10 billion-plus market worldwide, as more and more cancer immunotherapies are launched onto the market. It licenses the drug from the Spanish company Palau Pharma.
The UK firm is exploring the potential of POLB-001 to treat severe influenza, which can also trigger a runaway immune and inflammatory response, and its pipeline also includes an oral GLP-1 receptor agonist for obesity and diabetes, using a drug delivery technology from AnaBio Technologies, which is due to start first-in-human trials in the latter half of this year.
