PORTABLEMOLECULARDIAGNOSISOFHPV

CatherineKlapperich,Ph.D.Director,CenterforFuture

TechnologiesinCancerCareBostonUniversity

CervicalCancerandHPV

Whendiagnosedearlyandaccurately,cervicalcancerhasahigh5yearsurvivalrate,emphasizingthevalueofearlydetection.

Cervicalcanceristhefourthmostcommoncancerinwomenworldwideandkills266,000womenperyear.

Approximately87%ofthesecasesareindevelopingcountries,wheretherearelimitedresourcesforscreening.

HPVisthecausativeagentinmostcervicalcancers.

WHOGuidelinesforCervicalCancerScreening

What happens if there’s a positive test? Where does this fit in to the treatment chain?

ComponentsofaPortableMolecularDiagnostic

Sample Collection

Isolate nucleic acids

Amplify Nucleic Acids

Readout

Cao Q et al., PLoS ONE 7(3): e33176. (2012)

• 146 NPA and NPS samples were collected during 2008-2010 at Boston Medical Center (BMC) Beth Israel Deaconess Medical Center (BIDMC).

• Patients presenting with one or more of: fever, cough, sore throat, myalgia, nasal congestion, headache, malaise, or diarrhea.

• 12 months to 70 years.

• RT-PCR Chip for INFLA

DesignforPOC– DesignforMinimalInstrumentation

• Size

• Shelflife

•Passiveflow

•Heatwithminimal/no

instrumentation

• Intuitivereadoutwithoutinstrumentation

Goal:Getamoleculartesttoaremoteclinic.

NucleicAcidIsolation

Rodriguezetal.,Anal.Chem.,2015,87 (15),pp7872–7879

ValidationofAmplifiableNAAnalysisofLAMPinDifferentPapers

Linnes JC, Rodriguez NM, Liu L, Klapperich CM, Biomed Microdevices. 2016 Apr;18(2):30.

NucleicAcidAmplification

Isothermal Techniques LAMPHDA

DNAExtractedfromStool,AmplifiedwithoutInstrumentation

HuangS,etal.(2013),PLoSONE8(3):e60059.

60-65°C

Linnes,etal.,RSCAdv.2014Jan1;4(80):42245-42251.

Lysis,IsolationandAmplificationonPaperChlamydiaCells(DNA)

Readout

ClinicalInfluenzaASamples:IsothermalAmplificationandPaperReadout

Rodriguezetal.,Anal.Chem.,2015,87 (15),pp7872–7879

IntegrationforHPV16DetectioninCervicalSwabSamples

RunningtheChip

N.M.Rodriguez,etal.LabChip,2016,16,753-763

Results

N.M.Rodriguez,etal.LabChip,2016,16,753-763

MultiplexingHPV16andHPV18

JaneDx,Inc.IncubatingattheBUPhotonicsCenter

Rajan Dewar, M.D. Catherine Klapperich, Ph.D. Mario Cabodi, Ph.D. Natalia Rodriguez, Ph.D.

Customer&ValueChain• TargetCustomersandValueChainDynamics:

• USpathlabs/Consumerplay• GeneralstrategyforLMIC:

• Ministryofhealth• NGOs• Providers• Patients

• Firsttargetmarket: India• Privatepracticesanddistributorswillbuyfromusandselldirectlytopatients.• Wewillthustargetdistributors,privatepractice providers,thenstategovernment• distributors(price,performance)à users(price)

RevenueModel&PotentialMarketSize:• Reimbursement: LMICmarketsarehighlysegmented:

• Insurance/reimbursementstructurenearlynon-existent(country-dependent)

• WillpatientspayOut-of-pocketfortests?• India:growingmiddleclasspays100%oopfortestsalready• Verysensitive toprice

• RevenuePotential:India• Customerswouldpay$10distributorspertest(assuming100%markup);distributorsbuyfromJaneDXat$5pertest.

• Screeningguideline:Womenages35– 64,cytologyevery3years;344millionwomenareeligible forscreening

• Test110millionwomeneveryyearà $550M/yearpotentialrevenue

21

FeasibilityStudyLate2016

SriRamachandra

MedicalCollege

(MOU)

TamilNadu

JaneDx,Inc.

Boston,MA

1000patients,3monthPilot.IntegratedintoCurrentScreeningProgram.

TamilNadu– PilotProgram

Totalnumberoftargetwomenscreened:2,91,525+1,96,559$1.5perpatient

MorewomendiefromcervicalcancereveryyearinIndia thananywhereelseintheworld,accordingtotheCervicalCancer-FreeCoalition

JaneDx

POCTRNResourcesLeveraged

• CFTCCAlphaPrototypingCoretoMakeEarlyChipsforProofofConcept.

• CIMITPrimaryCareCenterPilotGrant• CIMITCRAASHCourseandMentorship• CFTCCClinicalNeedsAssessmentCoreforIndiaMarketResearch/ContactEstablishment.

• JHUSTICenterDiscussions/Mentorship/TrainingRe:SamplePreparationofCervicalSwabs.

Acknowledgements Current Lab Members Dr. Andy FanDr. Sharon WongNatalia RodriguezWinnie WongLena LiuConstantinos KetavatisGeorge PrattProf. Mario Cabodi

AlumniDr. Jacqueline LinnesDr. Jason KellerDr. Cassandra NoackSamantha ByrnesDr. Jaephil DoMichelle Wong Dr. Mincheol Kim Dr. Shichu Huang Nga HoDr. Qingqing CaoDr. Sonali MahalanabisDr. Jane ZhangDr. Arpita BhattacharyyaJared SaffieJake TruebMelike Karakaya

NIH U54 EB015403NIH R01 EB008268NIH R44 AI073221NIH R21 AI071261NIH R41 AI092913

www.bu.edu/cftccwww.bu.edu/klapperich