SY-1425, A Potent and Selective RARA Agonist, Reprograms AML Cells for Differentiation Along Distinct Lineages Uncovering PD Markers for Clinical Studies

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.

Pharmacodynamic and pharmacokinetic evaluation of SY-1425 (tamibarotene) in biomarker-selected acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients

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...

RARA Pathway Activation Biomarkers in Study SY-1425-201 Define a New Subset of AML and MDS Patients and Correlate with Myeloid Differentiation Following Ex Vivo SY 1425 Treatment

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.

Early Results from a Biomarker-Directed Phase 2 Trial of SY-1425 in Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) Demonstrate DHRS3 Induction and Myeloid Differentiation Following SY-1425 Treatment

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.

Successful Treatment with Bortezomib, Panobinostat, and Dexamethasone of Acute Myeloid Leukemia (AML) in 2nd Relapse After Allogeneic Stem Cell Transplantation (SCT): Therapy Selected Based Upon Results of a Personalized Flow Cytometric Screen for Drug

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.

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

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.

Ex Vivo Drug Response Profiling Defines Novel Drug Sensitivity Patterns for Predicting Clincal Therapeutic Responses in Myeloid Neoplasms

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.