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Mission Bio Tapestri Platform Identifies Novel Resistance Mechanisms with IDH Inhibitor TIBSOVO in Acute Myeloid Leukemias in Agios-led Study


Published in Blood Advances, the breakthrough single-cell technology resolved molecular patterns associated with treatment resistance, providing insights for potential combination therapies


SOUTH SAN FRANCISCO, Calif. (May 14, 2020) Mission Bio, Inc., the pioneer in high-throughput single-cell multi-omics and DNA analysis, today announced the publication of a biopharma-led study using its Tapestri® Platform to characterize therapy resistance mechanisms to the IDH1 inhibitor TIBSOVO® in patients with acute myeloid leukemia (AML). The study, led by researchers at Agios and leading global cancer institutes, reveals mutation co-occurrence patterns and rare clones driving resistance to targeted therapies, and could be used to generate potentially actionable biomarkers in clinical trials. The findings were published in Blood Advances, a peer-reviewed medical journal of The American Society of Hematology.


Mutations in isocitrate dehydrogenase (IDH) genes occur in about 20% of adult AML patients, and can cause normal bone marrow cells to develop into leukemia cells. TIBSOVO, or ivosidenib, is a targeted therapy for IDH1-mutated AML, and was the first in its class of IDH inhibitors to be approved in July 2018, and can prevent leukemic cells from proliferating. However, resistance to TIBSOVO remains a challenge, and little is known about the molecular mechanisms driving resistance. Bulk sequencing methods lack the precision and resolution required to characterize the complex biology of treatment resistance.


Agios leveraged the Tapestri Platform to fully characterize the clonal architecture of AML at the single-cell level, revealing mutation co-occurrence, clonal evolution patterns, and rare clones undetectable by bulk sequencing. A key mechanism of resistance discovered was the emergence of IDH2 mutations, which often co-occurred in the same cell as IDH1 mutations, suggesting that combination or sequential IDH inhibitors could be effective treatment strategies.


“While new IDH inhibitors have improved the treatment landscape of AML, the Tapestri Platform resolves the clonal complexity of IDH-mutated AML previously impossible with conventional sequencing methods,” said Mission Bio CEO Charlie Silver. “Single-cell analysis offers opportunities to improve biomarkers in drug development pipelines and the current treatment paradigm by combining novel therapies to prevent or delay resistance to these novel agents.”


These insights underscore the power of single-cell DNA analysis to provide high-resolution monitoring of patient response to targeted treatment, and uncover the potential to develop more impactful, dynamic therapies and combinatorial treatment options for those with AML.


About Mission Bio
Mission Bio delivers targeted solutions for high impact applications with the Tapestri Platform. The Tapestri Platform is the industry’s first and only single-cell multi-omics platform, enabling genotype and phenotype from the same cell, and precise detection of heterogeneity in disease progression and treatment response. Application areas include blood cancers, solid tumors, and genome editing validation.


Researchers at Stanford University, MD Anderson Cancer Center (MDACC), the University of California at San Francisco (UCSF) and the University of Pennsylvania (Penn) have all leveraged the Tapestri Platform to support their research for characterizing clonal dynamics in AML, identifying MRD, and monitoring treatment response and therapy resistance. The company’s award-winning technology is also leveraged by LabCorp and Onconova Therapeutics to enable more efficient clinical trials.


Named PM360’s 2019 Trailblazer Company of the Year, Mission Bio gives researchers a highly sensitive, targeted, and customizable solution to move precision medicine forward.


Media Contact:

Kathryn Ryan

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(631) 255-5281

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