Myelofibrosis (MF) is a rare blood cancer belonging to a group of disorders called myeloproliferative neoplasms. The underlying cause of MF is unknown. Previously published data by Oncode Investigator Rebekka Schneider (Erasmus MC) showed that tasquinimod, an experimental drug that was initially tested for prostate cancer – ameliorates myelofibrosis in an experimental MF mouse model. The data showed that treatment with this drug results in normal blood counts, reduction of fibrosis in the bone marrow and normalization of spleen size in this mouse model. That suggests that tasquinimod can act as a disease modifying agent in MF.

The now planned study will investigate tasquinimod given as monotherapy to patients with myelofibrosis who have previously been treated with a JAK inhibitor or who are ineligible for JAK inhibitor treatment. The trial will be conducted at sites in the Netherlands and in Germany, with HOVON as the sponsor of the trial.

Addressing an urgent clinical need

Patients with a rare and chronic type of blood cancer called myeloproliferative neoplasm (MPN) have a relatively normal quality of life. MPNs are a group of diseases in which the bone marrow makes too many red blood cells, white blood cells, or platelets. The disease can progress to fibrosis of the bone marrow (myelofibrosis/MF), which means replacement of blood-forming cells by scar tissue and failure of the body to produce blood cells. Bone marrow fibrosis significantly impairs the quality of life for patients and can lead to severe complications.

JAK inhibitors (Fedratinib/Ruxolitinib) are the only first line treatments currently available for patients with intermediate or high risk-fibrosis. However, many patients must discontinue JAK inhibitors due to drug-related cytopenias and development of therapy resistance. Second line therapies so far are only supportive or for symptomatic management. Therefore disease-modifying treatments which can improve cytopenia, splenomegaly (enlarged spleen) and bone marrow fibrosis in this disease stage are urgently needed.

Background to the clinical proof-of-concept study

In single cell analyses of the bone marrow funded through her Oncode base fund, Oncode Investigator Rebekka Schneider and her team at Erasmus MC initially identified a targetable biomarker (alarmin S100A8/S100A9) that can act as a predictive biomarker and a novel therapeutic target in one. In this 2021 issue of Oncode’s digital magazine, Schneider talked about this extensively, mentioning a then not named existing drug that acts on the alarmin. She then went on and at the end of the same month, published data showing that tasquinimod can act as a disease modifying agent in MF.

Schneider was awarded an Oncode CPoC grant, and with the support of Oncode’s valorization team, a global patent license agreement with Active Biotech was concludedfor the use of tasquinimod and other inhibitors of S100 in the treatment of myelofribrosis.