Development of a Novel Clinical Diagnostic Assay for Peripheral T-cell Lymphoma (PTCL)

Project Summary Abstract
Peripheral T cell lymphomaPTCLis a heterogeneous cancer that constitutes up toof all non Hodgkin
lymphomaNHLThe World Health Organization classification recognizes a number of distinct subtypes of
PTCL but the diagnosis of these different subtypes is challenging even for expert hematopathologistsFurthermoreof PTCL cases are not classifiable into any specific subtype at all using current
diagnostic methodsPatients with PTCL generally have a poor prognosis with current standard of care
therapyand no improvement in the outcome of PTCL patients has been achieved in the last two decadesHowevernovel therapies targeted to specific PTCL subtypes have recently begun testingsome with
spectacular resultsAccurate diagnosis of PTCL and its subtypes has therefore become essential to ensure
selection of the most appropriate and effective treatment for each individual patientThis project will
leverage seminal work performed by academic investigators associated with the Lymphoma Leukemia
Molecular Profiling ProjectLLMPPin which robust molecular gene expressionGEsignatures have been
identified that are unique to each major subtype of PTCLThe project will build upon this workutilizing it as
the basis for the creation of a commercial assay for routine clinical application to improve the diagnosistreatmentand outcomes of PTCL patientsHealthChart LLCa recently founded molecular diagnostics firm
focused on the development of novel diagnostic assays for niche indications in cancer and other diseaseshas licensed the intellectual property and patent portfolio associated with the academic work and is the
small business partner in these proposed studiesThe overarching goal of this PhaseSTTR proposal
is to transition theacademicPTCL diagnostic and prognostic GE signatures originally developed using
fresh frozen specimens analyzed with expression microarrays to an optimizedlocked down signature
applicable to formalin fixed paraffin embeddedFFPEspecimens analyzed on the NanoString nCounter
platformThe two Aims of this proposalAimIdentify a reduced set of transcripts and create a novel
model able to replicate the existingacademicdiagnostic and prognostic PTCL signatureAimConfirm the applicability of the refined diagnostic and prognostic PTCL gene signature sets on the
nCounter platformNanoStringfor the analysis of FFPE specimenswill create an optimized and
locked down PTCL signatureestablish performance specifications for inter lab reproducibilityand validate
the signature to a rigorous set of target metricsThese studies will enable application of the assay as a CLIA
lab offering at the end of Phasewhile positioning the PTCL assay for transition to Phasedevelopment as
an in vitro diagnosticIVDkit and possibly a companion diagnosticCDxfor novel and or existing PTCL
therapies Project Narrative
Peripheral T cell lymphomasPTCLare a heterogeneousdifficult to diagnose group of cancers that
constitute up toof all non Hodgkin lymphomasNHLand are associated with a poor prognosiswith no
improvement in outcomes over the past two decadesHowevernovel therapies targeted to specific subtypes
of PTCL have recently begun to undergo testingsome with spectacular resultsThis scientific proposal
describes the development of a novel clinical diagnostic test for commercial application that is designed to
reliably identify the subtypes of PTCLthus helping to ensure the selection of the most appropriate and
effective treatments for each individual patient and ultimately improving the outcomes of individuals with these
cancers