UK group Kymab has unveiled what it says are “remarkable” early stage results for its new antibody therapy KY1005 in animal models of acute graft-versus-host-disease (GvHD).
The data, presented at the American Society of Hematology Annual Meeting in San Diego, California, this week, show that KY1005 was able to damp the exaggerated immune response that causes acute GvHD following bone marrow transplants.
When combined with the immunosuppressant Rapamycinan – an established yet on its own insufficient therapy to prevent acute GvHD – KY1005 completely prevented signs any signs of the condition, and all animals survived to the end of the study. The two molecules interfered with separate cellular pathways resulting in the enhanced effect, the firm noted.
KY1005 binds to OX40L and blocks it from activating OX40, a protein that induces prolonged response in T-cells of the immune system, which can lead to the damaging effects of acute GvHD and autoimmune diseases. According to Kymab, findings of its experiments add to the body of evidence indicating that OX40L is involved in a range of both allo-immune and autoimmune diseases in which inappropriate T-cell responses are directed either towards a transplant, or towards a patient’s own tissues.
“These are unprecedented results for a prophylactic approach to controlling disease in bone marrow transplant,” said Dr Leslie Kean, a paediatric cancer specialist at the Seattle Children’s Research Institute.
“None of the treated animals showed signs of the disease and all were healthy to the end of the study: we were amazed as each set of data emerged. It is the first time that uniform, long-term disease-free survival has been seen in this model. All of the biochemical, histological and pathological measures for disease in this transplant model were stable in the treated animals. It is a remarkable result.”
“We have set the bar high in this study and results were outstanding – beyond our expectations,” added Dr David Chiswell, Kymab’s chief executive. “The acute GvHD model represents an aggressive disease and demands that any new candidate drug works convincingly against a robust T-cell response: it is about as tough a test as we can envisage.”
Human trials are set to begin sometime next year.
Given the promising results for prophylactic use of KY1005, the team has now begun to examine its potential use for treatment after acute GvHD onset, while the firm is also exploring its potential in a number of autoimmune diseases.
Just days ago Kymab announced that it has bagged £18 million in a round of series C financing to help it advance its proprietary pipeline of first-in-class therapeutic human monoclonal antibodies.
