MicroRNA Lab Tests for Cancer

About

Platform Technology for Personalized and Precision Treatment Decisions Curewize develops lab tests for improving cancer patients’ survival and overall outcome. Our custom designed platform technology measures microRNA (miRNA) profiles in patients’ biofluids. MiRNAs control gene activity, and are considered superior biomarkers for personalized treatment decisions due to their direct link to cancer mechanisms and stability in human biofluid and tissue samples. Curewize gains value from clinically validated and commercially adapted miRNA assay technology, and management experienced in developing and commercializing lab tests for prognosis and diagnosis.   Product Portfolio Curewize current product portfolio includes 1) ProALLBM for deciding on the intense or standard treatment of acute lymphoblastic leukaemia (ALL) patients within 3 days of diagnosis, 2) ProALLBL is used for frequent and long-term monitoring of ALL patients for risk of relapse during and after treatment and 3) PreMed, a companion diagnostic for deciding on NAMPT and PARP inhibitor treatment for blood and solid cancers.   ProALL for Acute Lymphoblastic Leukaemia (ALL) Treatment Decisions Acute lymphoblastic leukaemia (ALL) patients succumb to a wide range of chronic medical disorders affecting the brain, lungs, heart, reproductive system and more. The indirect exposure of normal cells to toxic chemotherapy and radiation is the cause of detrimental side effects. Therefore, doctors treat patients with either standard, intermediate or intense therapy for decreasing treatment toxicity, while ensuring the ALL patients’ chance of survival. ProALLBM ProALLBM is a prognostic assay for deciding on ALL patients’ treatment protocol. The assay is based on the measurement of three microRNAs in bone marrow (BM) samples taken at diagnosis of ALL patients. Currently, MRD lab tests are routinely used for measuring ALL patients’ response to induction treatment and for deciding on patients’ risk based treatment protocol. However, MRD is a very complex assay that can only be performed in a few central labs. MRD requires 2 to 3 bone marrow samples taken before and during induction therapy with results being available only after 4 to 12 weeks of treatment. ProALLBM requires 1 bone marrow sample taken at diagnosis with results available within 1 to 3 days of diagnosis. ProALLBM answers the unmet need for a more rapid, reproducible, standardized and cost saving lab test for personalized treatment decisions of patients. ProALLBM adds unique information on the ALL patient not found in pre-treatment predictive factors or MRD. ProALL was developed and validated on patients from Israel, Czech Republic and the Netherlands Curewize is nearing the completion of the validation of ProALLBM on a national clinical trial cohort from Europe. Avigad et al., Genes Chromosomes Cancer. 2016;55:328-339. ProALLBL ProALLBL is a blood test for frequent and long-term monitoring of ALL patients for molecular relapse. Findings presented at ASH 2016, demonstrated that the level of ProALL microRNAs in blood correlates with the level in BM and can predict ALL patients risk for relapse. The need for a monitoring test is evident with nearly 15% to 20% of young ALL patients eventually succumbing to relapse, resulting in relapsed ALL as being the 4th most common childhood malignancy. Once relapse occurs, only 30% to 50% of patients can be cured. Detection of relapse at an early stage of disease increases the ALL patients’ chances of survival. Yet, many oncology groups do not incorporate monitoring in their ALL treatment protocols, due to the labour intensity of MRD measurement and the invalidation of the feasibility of routine MRD monitoring. Reasons for invalidation of MRD monitoring are: a) The unsuitability of long-term monitoring by MRD, since 50% of relapses occur with new undetectable leukaemia clones; and b) Practical and humane limitation of frequent monitoring, especially in children, due to risk of anaesthesia, discomfort and practical difficulties posed by BM aspiration. Thus, a simple monitoring blood test for ALL would increase the practicality of testing ALL patients more frequently and eventually lead to prevention of relapse by means of pre-emptive treatment. Curewize is currently conducting a prospective clinical trial for the ProALL monitoring blood test. First preliminary results are expected by the beginning Q1-2018. Avigad et al., Blood. 2016;128:1736.   PreMed a Companion Diagnostic for NAMPT and PARP Inhibitor Cancer Treatment PreMed PreMed is a companion diagnostic assay based on the ProALL technology. The assay can predict solid cancer patients and ALL patients who will respond well to treatment by NAMPT and PARP inhibitors. Physicians will use the assay for detecting patients who can be effectively treated by the inhibitors. The ability of the miRNA biomarker to predict good response to the inhibitors was proven in- in vitro and in vivo models. NAMPT is the key enzyme that generates NAD+, an energy molecule used for cell activity. Cancer cells require high levels of NAD+ to maintain rapid growth. Thus, inhibition of NAMPT expression lowers the generation of NAD+ and holds great promise as a therapeutic strategy for cancer patients. The PreMed microRNA targets and stops the production of NAD+ molecules. Curewize preclinical tests showed that low levels of PreMed predicted better and highly effective response to NAMPT inhibitor treatment. PARP is a “DNA editor” correcting mistakes in DNA during the rapid replication of cancer cells. PARP protein activity consumes up to 80–90% of the intracellular NAD+ stores within seconds after detecting DNA damage. When NAD+ levels are high (low PreMed), PARP inhibitors are less effective, and patients are less responsive to PARP inhibition. Curewize is currently seeking a Pharmaceutical partner to co-develop PreMed as a companion diagnostic for the partner’s pharmaceutical product.