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Weaving a Tapestri in oncology
NEWTOWN, Pa. & SOUTH SAN FRANCISCO, Calif.—Onconova Therapeutics Inc. and Mission Bio announced in August a collaboration to utilize the Mission Bio Tapestri Platform for targeted single-cell DNA analysis to study Onconova’s lead candidate cancer therapy, rigosertib, through clinical trials.
As Darrin Crisitello, chief commercial officer at Mission Bio, tells DDNews, “Clinical trials are growing in complexity and are in need of precision biomarkers to reduce the time and costs associated with the drug development cycle. Broad-based sequencing methods lack the sensitivity necessary to monitor the evolution of cancer cells, to reveal how specific mutations drive disease progression or therapy resistance in patients.”
“With Mission Bio’s Tapestri Platform, researchers can uniquely detect rare cancer subclones and co-occurring cancer mutations at the single-cell level, offering a precise way to measure therapy response and disease progression. Through this collaboration, Onconova will utilize Tapestri’s insight into disease origins and paths of progression to investigate its novel cancer therapy, rigosertib,” he continues. “Through a series of clinical trials using Tapestri, Onconova will get one step closer to bringing rigosertib into the hands of doctors and clinicians and helping patients in need.”
A myelodysplastic syndrome (MDS) is one of various conditions that can occur when the blood-forming cells in the bone marrow become dysfunctional and produce an inadequate number of circulating blood cells. It’s frequently associated with the presence of blasts or leukemic cells in the marrow. This leads to low numbers of one or more types of circulating blood cells, and to the need for blood transfusions.
In MDS, some of the cells in the bone marrow are abnormal (dysplastic) and may have genetic abnormalities associated with them. Different cell types can be affected, although the most common finding in MDS is a shortage of red blood cells. Patients with higher-risk MDS may progress to the development of acute leukemia.
“In adding the Tapestri Platform to our research and development program, we are including the opportunity to study single cell clones in MDS and determine the sequence of genetic events and the influence of rigosertib on these events along with clinical outcomes. These studies have the potential to make a meaningful difference in the lives of patients in need,” said Dr. Steve Fruchtman, CEO of Onconova.
A key publication has demonstrated the ability of rigosertib to block cellular signaling by targeting RAS effector pathways. Onconova is currently in the clinic with oral and IV rigosertib, including single-agent IV rigosertib in second-line higher-risk MDS patients (pivotal Phase 3 INSPIRE trial) and oral rigosertib plus azacitidine in first-line higher-risk MDS patients (Phase 2).
“Rigosertib has the potential to be the first new higher-risk MDS treatment in more than 15 years, for a condition affecting an estimated 59,000 patients with low- and higher-risk MDS in the United States alone. Currently, oral rigosertib is being developed as a combination therapy together with azacitidine for patients with higher-risk MDS who require HMA therapy,” Crisitello explains.
“However, it’s estimated that 80 percent of patients who suffer from this disease have a mutation within their cells. The vast majority have more than one mutation and the significance of each mutation is not entirely known, especially when it comes to disease progression or response to HMA therapy. The Tapestri Platform can identify subclones that help monitor a patient’s response to rigosertib in clinical trials,” he says. “Based on these insights, Onconova can confirm the effectiveness of rigosertib in blocking the activation of Ras effector proteins that are responsible for mutations causing MDS.”
Ras proteins control cell proliferation, and mutation of this protein can lead to cancer in affected individuals. Ras is mutated in over 30 percent of patients with cancer, making it one of the most sought-after targets. Rigosertib blocks the activation of Ras effector proteins, thus modulating the Ras pathway. Onconova’s goal is to fully enroll INSPIRE, its Phase 3 clinical trial studying rigosertib in higher-risk MDS patients who fail the current standard of care, by year-end.
“Through single-cell genomics, we can identify mutations with far better resolution than that of traditional sequencing methods. This allows a view into each patient’s disease at a level never before achieved,” adds Crisitello. “Mission Bio’s goal is to continue analyzing and providing insights on the effectiveness of rigosertib in helping cure MDS. As Onconova continues to develop new therapies, Mission Bio hopes its one-of-a-kind technology serves as an asset in progressing clinical trials. Ultimately the two companies want to make a meaningful difference in the lives of patients in need.”
“We’re thrilled to be partnering with a leading biopharmaceutical company discovering and developing novel products to treat cancer. With our technology, Onconova can get an in-depth view of each patient’s disease at a level of precision never before achieved,” he concludes.