Resistance Mechanisms to FLT3 Inhibitor for AML Characterized Using Mission Bio's Tapestri Platform in Newly Published Study

SOUTH SAN FRANCISCO, Calif., March 10, 2021 /PRNewswire/ -- Mission Bio, the life sciences company delivering single-cell resolution multi-omics tools to accelerate discoveries and improve time-to-market for new therapeutics, has announced that its Tapestri Platform was used in a new study published Friday in Blood Advances to characterize the complex clonal heterogeneity that leads to treatment resistance of the FLT3 inhibitor quizartinib in patients with acute myeloid leukemia (AML).

Using the Tapestri Platform to perform single-cell DNA sequencing, the study characterizes the previously unmeasurable tumor heterogeneity and clonal evolution of AML through a period of treatment with the FLT3 inhibitor, quizartinib. Previously undetectable by bulk sequencing, the single-cell data revealed that quizartinib drove clonal selection for subclones containing on-target (FLT3) and off-target (non-FLT3) mutations. Significantly, quizartinib selected for clones with off-target Ras mutations, demonstrating for the first time that Ras pathway mutations are a mechanism of clinical resistance to quizartinib. The study also found high heterogeneity in FLT3 kinase domain (KD) mutations, the type of mutation that is most implicated in resistance to quizartinib.

This study adds to a growing body of work that demonstrates the value of single-cell DNA sequencing for uncovering resistance mechanisms to targeted therapies. It also highlights the potential for use of this technology in a clinical setting, where serial measurements can inform combination and dynamic treatment strategies that preemptively impede relapse.

The study was led by research teams University of California, San Francisco (UCSF), Johns Hopkins University, and University of Pennsylvania.

"Cancer is complex. It is heterogeneous and it is constantly changing," said Cheryl Peretz, MD, UCSF, first author of the study. "By understanding how the different cells that make up a cancer work together and evolve to evade treatments, we can unlock the potential to personalize therapies. This gives patients the ability to treat - or even avoid - relapse, redefining what's possible in precision medicine."

"Discoveries that further our understanding of clonal evolution and heterogeneity can lead to better treatments, from combination therapies to rapid adjustments in care plans," said Charlie Silver, CEO of Mission Bio. "Our Tapestri Platform is purpose-built to power the kinds of scientific discoveries that can lead to meaningful impacts in the health of patients. Congratulations to the teams involved in uncovering these significant insights into FLT-3 inhibitor resistance in AML."

Today's announcement is the latest of several published studies that have utilized Mission Bio's Tapestri Platform to power discoveries in blood-based cancers. A study led by St. Jude Children's Research Hospital into the combination of gene mutations associated with acute erythroid leukemia (AEL) was published by the American Society of Hematology in its scientific journal Blood in January 2021. The study measured multiplexed CRISPR edits and subsequent secondary mutations in individual cells using the Tapestri Platform, demonstrating the ability to manipulate genomes and then measure those manipulations at single-cell resolution — an innovative new approach to disease modeling. 

To learn more about Mission Bio and how their Tapestri Platform is helping science further its understanding of cancer and unlocking pathways to new treatments, visit missionbio.com.

About Mission Bio

Mission Bio is a life sciences company that accelerates discoveries and cures in oncology by equipping researchers with the tools they need to improve how we measure and predict our resistance and response to cancer therapies. Mission Bio's multi-omics approach improves time-to-market for new therapeutics, including innovative cell and gene therapies that provide new pathways to health. Founded in 2014, Mission Bio has secured investment from Novo Growth, Cota Capital, Agilent Technologies, Mayfield Fund, and others.

The company's Tapestri platform gives researchers around the globe the power to interrogate every molecule in a cell together, providing a comprehensive understanding of activity from a single sample. Tapestri is the only commercialized multi-omics platform capable of analyzing DNA and protein simultaneously, from the same sample at single-cell resolution.  The Tapestri Platform is being utilized by customers at leading research centers, pharmaceutical, and diagnostics companies around the world to develop treatments and eventually cures for cancer. To learn more, visit missionbio.com.

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