Scientific Posters

The combination of venetoclax (VEN) and a hypomethylating agent (HMA) such as decitabine (DEC) is frequently used in acute myeloid leukemia (AML) for patients unfit for standard chemotherapy. However, there is a subset of patients who do not clinically respond to such combination therapies. To identify VEN + HMA non- responders prior to treatment we developed an assay on our automated, high throughput (HTS) ex vivo drug sensitivity platform to predict how a given patient will clinically respond to DEC + VEN within an ongoing, open label, phase II clinical trial (NCT03404193) for patients with newly diagnosed elderly/unfit or relapsed/refractory (R/R) AML.

Pediatric acute myeloid leukemia (AML) is a rare disease with roughly 600 cases diagnosed in the United States each year with minimal improvement in clinical outcomes over the last few decades. Diagnostic pediatric AML samples were assayed using an ex vivo drug sensitivity test to determine the correlation between ex vivo drug response and clinical outcome, and to compare conventional chemotherapy to other drug combinations ex vivo.

Listen to the exciting results from Notable's collaboration with Texas Children's Cancer Center highlighting response prediction in a pediatric acute myeloid leukemia (AML) study that was presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting. The data was presented by Dr. Alexandra Stevens from Texas Children's and demonstrates the correlation of functional drug sensitivity screening using Notable’s predictive technology platform with the clinical outcomes of pediatric patients.

A subgroup of the patient samples was defined by an SE driving RARA, which co-occurred with SEs driving FOS and JUNB, or IRF8. FOS and JUNB form the AP-1 heterodimeric TF known to promote an immature cell state and the interferon regulatory factor 8 (IRF8) pathway has been implicated in AML pathogenesis.

SY-1425 (tamibarotene) is an oral, potent and selective synthetic RARα agonist previously approved for the treatment of relapsed/refractory acute promyelocytic leukemia (APL) in Japan. Given preclinical evidence of SY-1425 sensitive AML cell lines and patient samples with RARA pathway activation defined by elevated RARA or IRF8, SY-1425 is being...

We developed an epigenetic approach to profile the gene regulatory landscape of primary AML/MDS patient samples. A novel patient subset defined by RARA pathway activation was identified by super-enhancers (SEs) at the RARA and IRF8 gene loci.

Bone marrow biopsies (H&E) at 40x from screening (A) and C3D1 (B). Bone marrow aspirate (WG stain) at 100x from screening (C) and C3D1 (D). (A) Blasts (black arrows) occur in many small groups. Maturing myeloid cells (yellow arrows), erythroid precursors (red arrows) and megakaryocytes (blue arrows) are also present.

Notable Labs uses a flow cytometric-based assay to test a panel of FDA-approved chemotherapy and targeted agents—singly and in combinations using a custom robotic platform—to determine anti-cancer effect against individual patient’s tumor cells.

Blood or bone marrow samples were red blood cell lysed upon arrival, counted and resuspended at the appropriate concentration in proprietary serum free media with cytokines. The samples were then plated in 384 well microtiter plates and treated with drugs in triplicate (for each staining panel) using an Echo acoustic dispenser.

Myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia (AML) are clonal myeloid neoplasms for which limited conventional treatment options exist in the relapsed / refractory setting, especially for older patients.