JAK2 Inhibitor Shows Potent Activity In Cells From MPD Patients
Cytopia'ts lead JAK2 inhibitor compound CYT387 has demonstrated potent activity in cells isolated from patients with myeloproliferative disorders (MPDs).
MPDs are a series of diseases where there is over-production of particular cells within the blood stream. One of these conditions is polycythemia vera (PV) where patients have excess production of red blood cells in the body which can lead to life-threatening conditions such as hemorrhage, thrombotic events (eg stroke) and enlargement of the spleen.
There are few pharmaceutical treatments for MPD patients and consequent unmet clinical need. Progressive disease can lead MPD patients to develop leukemia or myelofibrosis.
Over 95% of patients with PV and about 50% of patients with two related MPDs, essential thrombocythemia and primary myelofibrosis, possess a genetic mutation which causes over-activation of the enzyme JAK2. Cytopia is developing selective and potent inhibitors of the JAK2 enzyme to block excessive activity.
Cytopia has collaborated with leading laboratories in this field including the Royal North Shore Hospital in Sydney, Australia and the Mayo Clinic in Cleveland, USA to study the effects of its JAK2 inhibitors in pre-clinical studies on MPD patient cells.
The data obtained in these studies show that Cytopia's compounds block the mutant JAK2 enzyme and thereby inhibit, in the case of PV, the over-production of red blood cells. Additionally, when normal human cells were tested in the same assay, Cytopia's JAK2 inhibitor showed a possible therapeutic window with a greater potency inhibition of disease cells. Extensive screening against a panel of 73 kinase enzymes indicates that CYT387 possesses selectivity for JAK2, potentially minimizing off-target toxicity.
Dr Pardanani of the Mayo clinic said: "In ex vivo studies, we have seen encouraging preliminary results with Cytopia's compounds including the inhibition of erythroid colony growth from PV patients harboring the JAK2 V617F mutation."
Cytopia's Research Director Dr Chris Burns stated: "This data is important validation that our selective JAK2 inhibitors stop the proliferation of mutant cells from patients with these diseases at clinically achievable doses."
Cytopia is developing JAK2 inhibitors for the treatment of MPDs and other solid and blood cancers. In addition, other inhibitors of JAK2 are under development for cardiovascular and ophthalmic diseases.