9 February 2022
New CPoC grant brings new hope for patients with myeloproliferative neoplasms and bone marrow fibrosis
Oncode Institute aims to link fundamental and clinical research to enable efficient translation of promising findings into novel diagnostic methods and clinical treatment strategies. Oncode created the Clinical Proof-of-Concept (CPoC) fund to support the clinical translation of Oncode’s fundamental research, and is now pleased to announce that the 16th grant within the CPoC programme has been awarded.
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 and can lead to 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.
A predictive biomarker and a novel therapeutic target in one
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 the April 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 – an experimental drug that was initially tested for prostate cancer – ameliorates the disease 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. And that suggests that tasquinimod can act as a disease modifying agent in MF.
Schneider - together with clinical PIs Peter te Boekhorst (Erasmus MC) and Martina Crysandt (RWTH Aachen) - was now awarded an Oncode CPoC grant, and with the support of Oncode’s valorization team, has entered into a global patent license agreement with Active Biotech – for the use of tasquinimod and other inhibitors of S100 in the treatment of myelofribrosis. Active Biotech and Erasmus MC will initiate a research collaboration related to use of tasquinimod in MF, that includes pre-clinical as well as the clinical proof of concept study in patients with MF The clinical study will be funded through the CPoC grant.
‘We are thrilled that we can get a clinical trial started based on our findings from single cells sequencing which was also funded by Oncode. It was always my dream that our findings in the lab will be translated to better outcomes in patients and hopefully help to ameliorate the life-threatening condition of bone marrow fibrosis’ says Schneider.
Using the CPoC grant, her team will target the alarmins S100A8/S100A9 with the small molecular oral inhibitor tasquinimod, with the primary objective of finding out whether this reduces splenomegaly, and also ameliorates cytopenia and decreases fibrogenic stimuli even in a progressed disease stage, thus improving the significantly impaired quality of life of patients with MF and potentially increasing the overall survival.