In vitro and in vivo evaluation of elephant p53 (EP53) protein nanoparticles for pediatric osteosarcoma

PROJECT SUMMARY ABSTRACT
PEEL TherapeuticsIncis a life sciences company created to impact the lives of people with cancerBased on
the research efforts of DrJoshua Schiffman and DrAvi SchroederPEEL TherapeuticsPEELhas created
liposomal nanoparticles that have been loaded with elephant pEPproteins as a new class of anti cancer
protein therapeuticsElephants have an unexpectedly low rate of cancer given their large sizetimes that of
humansand longevitylifespans oftoyearsWhen exposed to DNA damageelephant cells undergo
much more robust ptriggered apoptosiscell deathcompared to human cellseffectively eliminating precancerous cells with DNA mutationsRecent work has shown that human cancer cells undergo rapid and robust
cell death when the EPprotein is transduced and expressedThis EPinduced apoptosis is especially
pronounced in human osteosarcoma cellsone of the most common and deadly pediatric bone tumorsEPprotein delivered by PEELandapos s nanoparticlesNPsinduces apoptosis in osteosarcoma cells in vitroOsteosarcoma has not had a successful new therapeutic drug in overyears and represents a very large and
unmet clinical needFor this Phase I STTR programPEEL Therapeutics will move forward with testing of its
EPprotein NPsand also will determine if adjuvant chemotherapy delivered prior to EPNP treatment
increases the ability to kill cancer cellsFor AIMPEEL will select the most effective dose EPprotein loaded
nanoparticles to cause apoptosis in different types of osteosarcoma cellswith and without adjuvant
chemotherapyin vitroFor AIMPEEL Therapeutics will identify the maximum tolerated doseMTDfor EPprotein loaded nanoparticles and demonstrate their efficacy in osteosarcoma patient derived xenograftPDXmodelsin vivoAfter completing these Phase I STTR tasksPEEL Therapeutics will be in an excellent position
to advance its new and patented nanoparticle protein drug on the pathway to further preclinical studieseventually culminating in first in human trialsThese efforts by PEEL Therapeutics will lead to clinical
improvements for the outcome of children and adolescents being treated for osteosarcomaa deadly bone
tumor currently lacking new therapeutic options PROJECT NARRATIVE
Osteosarcoma is one of the most common and deadly pediatric bone tumorsand has not had a successful new
therapeutic drug in overyearsPEEL Therapeutics has manufactured novel elephant pEPproteinloaded nanoparticles that deliver elephant cancer resistance proteins directly to tumor cellsFor this Phase I
STTR programPEEL Therapeutics will demonstrate the efficacy of EPnanoparticle treatment in live animals
with implanted osteosarcoma tumorscanine and humanand collect the data that is needed to move closer to
a new treatment option for children and adolescents with osteosarcoma