Abstract

Malignantmelanomaisoneofthemostaggressivetypesofskincancer,causingalarge majorityofskin-cancerrelateddeathsworldwide.Thecombinationofanti-PD-1andanti-CTLA-4 isFDAapprovedformetastaticmelanomaandshowsbetterefficacythananysingleagent alone.Unfortunately,theincidenceofhigh-gradeimmune-relatedadverseevents(irAEs)dueto anti-CTLA-4isapproaching50%.Thereisapressingclinicalneedtodeveloptherapeutic agentsthatmayenhancethetherapeuticeffectofanti-PD1therapywithoutsignificantly increasingtoxicityincancerpatients. CureBiotechisaimedtodevelopanefficacious intratumoralimmunotherapeuticdrugthatcantreatmetastaticmelanomabyitselfandin combinationwithanti-PD1therapy.Resiquimodisatoll-likereceptors(TLR)7and8agonist.It isasecondgenerationimidazoquinolinethatis100timemorepotentthanimiquimod (Aldara). Usinga phaseISBIRgrant,CureBiotechhasdevelopedtwoproprietaryhydrogelbased injectableformulationsforresiquimod.Theformulationsweredesignedtoconfineresiquimod locallyinthetumortodecreasesystemiccytokinereleasesymptoms;?andtobepenetratebetter fibrotictumorstromatoallowastrongerhostimmuneresponse.Ourpreliminarydata demonstratesthatresiquimodtreatmentnotonlyinhibitedmelanomagrowth,butalso suppressedlymphnodemetastasis.Resiquimodincreasesthenumberofintra-tumoralCD45+ leukocytesandenhancestheproliferationandfunctionoftumorantigenrecognizingCD8+ effectorT-cells.Resiquimodshowssynergisticeffectininhibitingmelanomagrowthwhen combinedwithanti-PD1therapy.ThisSBIR phaseIIprojectisaimedto1)studyPD/PKofthe formulatedinjectableresiquimodinmelanomamousemodels;?2)optimize dose/frequency/timingofformulatedresiquimodincombinationwithanti-PD1therapyfor melanoma;?3)performnon-clinicalINDenablingstudiesusingformulatedinjectableresiquimod. ThedeliverablesproposedinthisSBIRgrantrepresentthejumpingstonetowards(i) submissionofFDAINDapplicationofaninjectableresiquimodformulationand(ii)attracting privateequityfundingtosupportPhaseIclinicaltrialofinjectableresiquimodinpatientswith metastaticmelanoma.CureBiotechhasthebusinessdevelopmentexpertise,properintellectual propertyandscientificandpersonnelcapabilitytoachievetheseaimsquicklyandmeticulously. ResultsfromthisproposalwilllayasolidfoundationforFDAINDsubmissionthatwillultimately bringanovelandeffectivetherapytocliniciansandpatientsintheirfightagainstmelanoma.

Public Health Relevance

PROJECTNARRATION Resiquimodisapowerfulimmuneresponsemodifierthatstimulatesthebody?sownimmune systemtoattackcancercellsthroughactivationoftoll-likereceptors7/8.Inourproposed project,wewillstudyPD/PKoftheformulatedinjectableresiquimodinmelanomamouse models;?optimizedose/frequency/timingofformulatedresiquimodincombinationwithanti-PD1 therapyformelanoma;?andperformnon-clinicalINDenablingstudiesusingformulated injectableresiquimod.CureBiotechisaimedtodevelopanefficaciousintratumoral immunotherapeuticdrugthatcantreatmetastaticmelanomabyitselfandincombinationwith anti-PD1therapy.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
2R44CA217489-03
Application #
9678447
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Franca-Koh, Jonathan C
Project Start
2017-03-06
Project End
2021-02-28
Budget Start
2019-03-06
Budget End
2020-02-29
Support Year
3
Fiscal Year
2019
Total Cost
Indirect Cost

  Institution

Name
Curebiotech, Inc.
Department
Type
DUNS #
080612258
City
Philadelphia
State
PA
Country
United States
Zip Code
19146