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Curewize Preparing Test for Guiding ALL Treatment Decisions for 2019 European Launch

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NEW YORK (GenomeWeb) – Curewize Health, an Israeli molecular diagnostics company, aims to have a test for guiding treatment decisions in acute lymphoblastic leukemia patients on the European market by the beginning of next year, according to CEO Jennifer Yarden.

The five-year-old firm recently completed a clinical trial of the real-time PCR-based test, called ProALL-BM, on patients from a European National Registry Study. ProALL-BM profiles microRNA biomarkers in bone marrow obtained from ALL patients. Based on the presence or absence of these markers, the test stratifies the patients into risk-based treatment groups.

Curewize claims that its test provides information related to the possibility of relapse in ALL patients, identifying patients that are at a high risk of relapse before starting treatment.

The recent clinical trial was carried out in collaboration with the Italian Association of Pediatric Hematology and Oncology (AIEOP) on roughly 270 samples. A paper detailing the study is forthcoming, Yarden said.

Given the completion of the clinical trial involving a European cohort, the Yokneam-based company is on track to secure a CE-IVD mark for ProALL-BM during the first quarter of 2019. The company will then approach national oncology groups within Europe, such as the AEIOP, with the hope they will evaluate the assay and possibly integrate it into their risk assessment protocols.

"We want to offer this test to national oncology groups to try with their protocol," said Yarden. "Once they consider this test to be a good one to use, we hope they will adopt it," she said.

Curewize is looking to make ProALL-BM kits available to laboratories within Israel in order to encourage adoption of the test next year. The firm is also exploring options for making the assay available in the US, as well to collaborate with partners in the pharmaceutical industry on potential companion diagnostics.

In terms of rolling out ProALL-BM in the US, Yarden said that the company will most likely look to partner with a CLIA-compliant lab. She said that in the meantime Curewize is discussing a possible study of the test with an American medical research group. She declined to provide a timeline for US market entry.

Yarden co-founded Curewize in 2013. She formerly served as director of clinical development at Glycominds, an Israeli molecular diagnostics firm that specializes in blood-based assays for gastrointestinal diseases. Curewize CTO Nit Dotan also served previously as CTO of Glycominds. The company commenced activities in 2015 after receiving roughly $1 million in funding through the Israel Innovation Authority Incubator Program and Youdim Pharmaceuticals. As part of the grant, which is set to run through the end of this year, Youdim has provided Curewize with facilities and professional assistance.

The biomarkers -- miR451 and miR151-5p -- used in ProALL-BM were licensed from Mor Research Applications, the technology transfer office of Kupat Holim Clalit, the largest health management organization in Israel. The markers were discovered by Isaac Yaniv, Smadar Avigad, and Keren Shichrur, all investigators at Schneider Children's Medical Center of Israel in Petah Tikva. Yaniv and Avigad continue to advise the firm, while Shichrur served as its product development specialist.

The researchers described the development of the miRNA markers in a 2016 Genes, Chromosomes, & Cancer paper.

Those miRNA markers are at the core of ProALL-BM, Curewize's flagship assay, which measures their levels in samples obtained at the time ALL is diagnosed in patients before starting treatment. The test is being positioned to streamline the treatment decision-making process, while also factoring in the risk of relapse. Typically, risk of relapse is determined by quantifying leukemia cells in patients several months after they begin a treatment regimen. Curewize is therefore marketing its test as a means to obtain that information prior to commencing treatment.

According to Yarden, ProALL-BM can be run using conventional RT-qPCR platforms. "It's a nice, simple test that can be used in molecular and clinical labs around the world," she said. Yarden added that Curewize is considering developing a point-of-care test in the future, though such a platform would require additional investments in software and hardware.

In terms of competitors, one potential rival is Seattle-based Adaptive Biotechnologies, which sells a next-generation sequencing-based assay called clonoSeq for detecting and quantifying measurable residual disease in lymphoid malignancies. Those with lower levels of cells typically receive standard treatment, while those with higher levels of cells go on to more intense treatments. The test was originally developed by South San Francisco, California-based Sequenta, which Adaptive acquired in 2015.

While Yarden conceded that Adaptive Bio's approach has its merits, she noted that it is run on patients following treatment, as opposed to before a treatment plan has been decided. She also said that Curewize's miRNA-based assay supplies information on patients that is not obtained by other biomarkers. "MicroRNA regulate gene activity, so measure a different aspect altogether," Yarden said. "We add important information."

Curewize is also developing a blood-based version of its ProALL test, called ProALL-BL. According to Yarden, the assay in development could be used for monitoring ALL patients before, during, and after treatment. "Patients would much rather have a blood test than a bone marrow test," noted Yarden.

She said that ProALL-BL is undergoing clinical trials in Israel at Schneider Children's Medical Center as well as the Rambam Health Care Campus in Haifa.

The test relies on the same markers as ProALL-BM. Yarden said that preliminary findings from the study have demonstrated its feasibility, but she didn't provide further details.

Another test in the firm's pipeline is a companion diagnostic for deciding on the treatment of solid cancers with NAMPT and PARP inhibitors. She did not provide a timeline for when the test might become available.