How We Capture Mechanism of Action in the Notable Platform

Notable has developed a versatile platform for testing a wide variety of drugs in patient ex vivo clinical samples, with a high-throughput flow cytometry readout that incorporates diverse phenotypes, including measures of apoptosis, proliferation, differentiation, and stemness, as well as immunotherapy targets.

Getting the right cancer drugs to the right patients relies on the accurate prediction of clinical response to an ever-increasing array of cancer therapies.

Notable’s Mission to Move Beyond a “One-Size-Fits-All” Ex Vivo Drug Sensitivity Test

Figure 1: Heatmap showing responses to 31 drugs or drug combinations (rows) in 37 blood cancer patient samples (columns). Each colored box represents the level of ex vivo drug sensitivity, with red indicating the highest level of sensitivity and blue the lowest. Getting the right cancer drugs to the right patients relies on the accurate […]

Notable Appoints Biotech Veteran Joseph Wagner PhD as Chief Scientific Officer

FOSTER CITY, CA – July 08, 2020 (GLOBE NEWSWIRE) – Notable, which is redefining cancer treatment by taking a functional approach to precision oncology in hematological cancers, announced today that Joseph Wagner, PhD, has joined the company as Chief Scientific Officer. Dr. Wagner.

Ex Vivo High-Throughput Flow Cytometry Screening Identifies Subsets of Responders to Differentiation Agents in Individual AML Patient Samples

Prognoses for acute promyelocytic leukemia (APL) patients improved drastically upon the introduction of differentiation therapy with all-trans-retinoic acid (ATRA) in combination with conventional chemotherapy. Unfortunately, this therapeutic approach has not translated to other genetic subtypes of acute myeloid leukemia...

PTC299 Is a Novel DHODH Inhibitor That Modulates VEGFA mRNA Translation and Inhibits Proliferation of a Broad Range of Leukemia Cells

To identify cancer cell types that are sensitive to PTC299, a panel of 240 tumor cell lines was tested against which the concentration of compound required to reduce cell viability by 50% (CC50) was determined. Overall, the viability of 18% of cells from solid tumor(34/184) and ~57% of cells from hematologic malignancies (32/56) was reduced...

Single-cell mutational profiling of clonal evolution in myelodysplastic syndromes (MDS) during therapy and disease progression

The barcodes were then used to reassemble the genetic profiles of cells from next-generation sequencing data. We applied this approach to sequential clinical MDS samples, genotyping the most clinically relevant loci across more than 15,000 individual cells. Additionally, to study effects of subclonal mutations on drug sensitivity, ex vivo functional...

Recurrent drug sensitivity patterns in myelodysplastic syndrome patients are recapitulated by ex vivo drug response profiling

Myelodysplastic syndromes (MDS) are a collection of clonal diseases of dysfunctional hematopoietic stem cells, characterized by ineffective hematopoiesis, cytopenias, and dysplasia. Limited conventional treatment options exist for these patients, with hypomethylating agents remaining the standard of care for higher-risk MDS patients.

Molecular pathophysiology of the myelodysplastic syndromes: insights for targeted therapy

The clinical heterogeneity of the myelodysplastic syndromes (MDSs) relates to the recently discerned panoply of molecular abnormalities extant within this disease spectrum. Despite increasing recognition of these biologic abnormalities, very limited therapeutic options exist to exploit our increasing understanding of the molecular pathophysiology of MDS.

Ex Vivo Drug Sensitivity Profiling In Myelodysplastic Syndrome (MDS) Patients Defines Novel Drug Sensitivity Patterns For Predicting Clinical Therapeutic Outcomes

We performed drug sensitivity profiling on 60 patient samples in both newly diagnosed and treatment-refractory myeloid neoplasms (46 MDS, 4 CMML, 10 AML). Fresh bone marrow aspirates and/or peripheral blood specimens were RBC-lysed and re-suspended in serum-free media with cytokines.

A Feasibility Study of Biologically Focused Therapy for Myelodysplastic Syndrome Patients Refractory to Hypomethylating Agents

We performed a prospective feasibility study in 21 patients with HMA-refractory MDS enrolled at Stanford University from April 2018 through March 2019. All patients had a baseline bone marrow (BM) biopsy with BM aspirate and peripheral blood (PB) samples sent for mutation testing (596-gene panel, Tempus, Chicago, IL) and ex vivo DSS (Notable Labs, Foster City, CA).