GENReports: Market & Tech...

GENReports:,Market,&,Tech,Analysis,!Produced!by!Enal!Razvi,!Ph.D.!©!2015,GENengnews.com,

> Enal Razvi, Ph.D. Biotechnology Analyst, Managing Director Select Biosciences, Inc. [email protected]!

GENReports: Market & Tech Analysis


•  The,focus,of,this,GEN,Market,&,Tech,Analysis,Report,is,to,frame,a,very,Amely,and,expanding,development, in, the, life, sciences,field:,,The,PotenAal,of,Liquid,Biopsies,

•  A,major, current, challenge, in, the, cancer, biomarkers, field, is, that,samples, of, tumor, Assue, need, to, be, harvested, in, order, to,understand,somaAc,mutaAons,as,a,means,to,target,therapies.,,This,is,the,premise,of,cancer,precision,medicine.,

–  The! challenge! is! that! these! ?ssue! biopsies! tend! to! be! invasive! and! costly! [in!terms!of!procedure!costs,!hospital!stays,!and!loss!of!produc?vity]!

–  Furthermore,! pa?ent! compliance!with! these! procedures! is! variable! given! their!invasive!nature!as!well!as!discomfort!

–  Finally,! these! invasive! ?ssue! biopsies! cannot! be! performed! longitudinally! over!?me!and!therefore!the!informa?on!about!the!progression!of!a!disease!process!is!lost!

–  These! are! the! drivers! for! the! development! of! liquid! biopsies!! MinimallyIInvasive!means!for!Harves?ng!Biomarkers!from!Pa?ents!for!Disease!Monitoring!

Why,Liquid,Biopsies?!

MinimallyMInvasive,Means,for,HarvesAng,Biomarkers,from,PaAents,for,Disease,Monitoring,Over,Time,


•  The!choice!of!analytes!which!need!to!be!enumerated/analyzed!in!biofluid!biopsies!is!currently!controversial!given!that!different!classes!possess!dis?nct!features!and!benefits!

•  The,different,classes,are,as,follows:,1.   CirculaAng,Tumor,Cells,(CTCs),2.   CirculaAng,Nucleic,Acids,3.   CirculaAng,Vesicles,(such,as,Exosomes,or,Microvesicles),

Containing,Biomarker,Cargo,4.   CirculaAng,Proteins,

•  Each!of!the!above!analyte!classes!has!advantages!and!disadvantages!as!discussed!in!the!next!page,

CirculaAng,Biomarkers,Enable,Liquid,Biopsies!

Which,is,the,Best,Analyte,Class,for,Liquid,Biopsies?,SAll,Unclear,,MostMLikely,a,CombinaAon,Assessing,Various,Aspects,of,

Disease,and,Different,for,DisAnct,Disease,Classes,


•  One!of!the!challenges!in!the!development!of!biofluid!biopsies!is!the!“sample!prepara?on”!on!the!frontIend!from!clinicallyIrelevant!pa?ent!samples!

•  Currently,,the,most,commonly,studied,biofluid,samples,are,–  Whole!Blood!–!for!CTC!Capture!–  Plasma!–!for!Extracellular!Vesicles!(EVs)!and!Extracellular!Nucleic!

Acids!!–  Serum!–!for!Extracellular!Vesicles!(EVs)!and!Extracellular!Nucleic!

Acids!–  Urine!–!for!Extracellular!Vesicles!(EVs)!and!Extracellular!Nucleic!

Acids!•  Less,common,biofluid,classes,currently,

–  Cerebrospinal!fluid!(CSF)!

Which,Biofluid,Class,to,UAlize,for,a,Liquid,Biopsy?!

Which,is,the,Best,Analyte,Class,for,Liquid,Biopsy,Development:,SAll,Unclear,,MostMLikely,a,CombinaAon,Assessing,Various,Aspects,of,Disease,and,Different,for,DisAnct,Disease,Classes,based,on,Anatomy,


Comparison,of,Various,Classes,of,CirculaAng,Biomarkers,visMàMvis,their,Suitability,for,Liquid,Biopsy,Development,

Exosomes,,Microvesicles,

CirculaAng,RNA,

CTCs, CirculaAng,CellMFree,DNA,

Tissue,Sample,[as,a,Benchmark],

Sample!Availability!Throughout!the!Disease!Process!

Yes, Yes, Only,in,Late,Stages, Yes, Invasive,Procedures,for,Harvest,

Sample!Stability!When!Maintained!Ex#Vivo#[ie.,!postIexplant]#

Stable, Stable, Unstable, Stable, Stable,when,processed,,

U?lity!for!Longitudinal!Disease!Monitoring![ie.,!ability!to!harvest!samples!from!pa?ents!over!?me]!

Yes, Yes, Yes,with,caveats,[ie.,,late,stages,more,amenable],

Yes,with,caveats,[ie.,,late,stages,more,amenable],

Invasive,Procedures,for,Harvest,

Clinical!U?lity!as!a!Biomarker!

Not,Demonstrated,

Not,Demonstrated,with,excepAons,

Only,Demonstrated,in,Specific,Disease,

Classes,

Not,Demonstrated,with,excepAons,

Yes,

Suitable,for,Liquid,Biopsy,

Development,

Yes, Yes, Yes, Yes, No,


Various,Sources,of,CirculaAng,Biomarkers:,Analytes,for,Liquid,Biopsies!

Placental, fetal cells

(utilized in NIPT)

Circulating tumor cells

(CTCs)

Activated lymphocytes and other nucleated

cells

Lysis

Necrosis

Apoptosis

Source:!Pamela!Pinzani,!Univesità degli Studi di Firenze.!


Classes,of,Extracellular,Vesicles,(EVs):,PotenAal,for,Liquid,Biopsy,Development,

"  Extracellular,vesicles,(EVs),represent,a,source,of,circulaAng,biomarker,cargo,encapsulated,in,a,lipid,coat,

"  There,is,extensive,diversity,of,size,and,biomarker,cargo,within,the,EVs,suggesAng,that,different,classes,may,have,potenAal,for,liquid,biopsy,development,in,different,disease,classes,–,oncosomes,,for,instance,,associated,with,various,cancers,

"  Harvest,and,interrogaAon,of,EV,biomarker,cargo,for,liquid,biopsies,

EV,Size,DistribuAon,May,Reflect,FuncAonal,Significance,


CirculaAng,DNA,(cfDNA,,ctDNA),as,a,CirculaAng,Biomarker,for,Liquid,Biopsies,

"  Cancer,is,the,Driver,"  5M7,ng,per,mL,of,plasma,"  More,concordance,with,

clinical,progression,than,CTCs,

"  The,cancerMfocused,pharmas,are,evaluaAng,by,performing,NGS,on,cfDNA,to,look,for,cancer,mutaAons,

"  Development,of,Liquid,Biopsies,

"  PotenAal,CompeAtor,to,Extracellular,Vesicles,and,CTCs,as,CirculaAng,Biomarkers,

"  Figure,Source:,Jonathan,Bailey,,NHGRI,


Source:,Luis,Diaz,et#al.,,www.ScienceTranslaAonalMedicine.org,19,February,2014,Vol,6,Issue,224,224ra24,

Clinical,UAlity,of,ctDNA,

In,Many,Cancer,Classes:,

Note,that,many,cancers,demonstrate,detectable,ctDNA,,ie.,,the,use,of,ctDNA,

for,disease,monitoring,is,

potenAally,across,many,cancer,classes,,


Challenges,and,OpportuniAes,in,the,Liquid,Biopsy,Space!

Classes of Circulating Biomarkers

Downside Upside

"  CirculaAng,Free,DNA,(cfDNA),

"  CirculaAng,microRNAs,[freely,circulaAng,or,enveloped,within,exosomes],

"  CirculaAng,mRNAs,[enveloped,within,exosomes],

"  CirculaAng,Oncoproteins,

"  CirculaAng,Exosomes,,Microvesicles,

"  CirculaAng,Tumor,Cells,(CTCs),

"  Identification of potential biomarkers associated with disease are required – This is Difficult

"  Minimally-invasive diagnostics development

"  Samples are reflective of the in vivo situation in the patient as opposed to a “segment” of the tumor

"  Appropriate samples that are indicative of disease

"  Robust assays/approaches to characterize the circulating biomarkers in the liquid biopsy samples

"  Longitudinal analyses of patient response to therapies [such as cancer therapeutics] without the need for costly, painful invasive procedures

"  Identifying those that are the most relevant with prognostic and/or predictive value

"  Acceleration of adoption of precision medicine

"  Demonstration of clinical relevance for prognosis in the absence of large, multi-year prospective clinical trials of patient survival

"  Tissue Specificity of Origin of Disease can be Studied


Liquid,Biopsies,will,Move,to,the,PointMofMCare,(POC),Sekng,Eventually!

•  There! is! moun?ng! evidence! that! liquid! biopsies! will!migrate!towards!the!“pointIofIcare”!(POC)!sebng!for!the!following!reasons!–  Beyond! cancer,! biofluids! may! be! harvested! for! other! disease! classes!

including! trauma?c! brain! injury! (TBI)! where! biopsies! of! the! brain! are!not!feasible!and!biofluids!offer!an!important!alterna?ve!–!diagnoses!of!TBI!must!necessitate!movement!towards!the!POC!sebng!

–  If!biofluids!are!to!be!deployed!for!rou?ne!cancer!screening!in!otherwise!“clinicallyIhealthy”! subjects,! this! of! course! must! be! performed! in!doctor’s!offices,!outpa?ent!clinics!–!the!“POC”!sebng!

–  Technology! development! for! POC! diagnos?cs! such! as! smartphoneIbased! diagnos?cs! is! proceeding! at! a! rapid! pace! and! we! believe! that!these! technologies!will! impact! biofluidIbased! diagnos?cs! especially! in!resourceIlimited!sebngs!and!for!public!health!


The,Liquid,Biopsies,Space,is,AlracAve,and,Evolving!

•  This!GEN!Report!provides!a!snapshot!of! the! liquid!biopsy!field!which! is!being!driven!by!the!various!classes!of!circula?ng!biomarkers!which!have!been!described!and!are!currently!being!evaluated!for!their!clinical!u?lity!

•  There! is!currently!a! race!as! to!which!biomarker!class!will!be!the! leader!for!liquid!biopsies!

–  CTCs!have!an!early!lead!in!this!game!with!the!US!FDA!approval!of!Veridex/Johnson!&!Johnson!CellSearch®!system!for!CTC!enumera?on!

–  However,!CTC!enumera?on!may!not!provide!a! comprehensive!picture!of! a!pa?ent’s!status!and!therefore!the!search!con?nues!for!other!analyte!classes!

–  This!is!where!circula?ng!DNA!and!exosomes/microvesicles!enter!the!picture!!!There!is!the!need!for!prospec?ve!clinical!trials!assessing!the!clinical!u?lity!of!these!biomarker!classes!for!biofluid!biopsies!!!S?ll!a!controversial!field!

–  Given!the!huge!interest! in!liquid!biopsies!based!on!academic!research!developments![exosome!and!cfDNA/cfRNA,!for!instance],!and!pull!from!the!companies!interested!in!developing! minimallyIinvasive! diagnos?cs,! there! is! much! ac?on! expected! over! the!coming!years!in!this!space!


Biofluid Biopsies and High-Value Diagnostics 2015 Boston – November 16-17, 2015

"  Dedicated!Conference!on!Liquid!Biopsies!"  All!Key!Opinion!Leaders!(KOLs)!from!Around!the!World!

Akending!and!Presen?ng!"  Network!and!Engage!with!KOLs!–!All!Classes!of!Liquid!

Biopsies!Represented!"  Please!Scan!QR!Code!with!iPhone/iPad/Android!to!Navigate!

to!Conference!Website!with!All!Conference!Details!


Exosomes and Liquid Biopsies Asia 2016: April 7-8, 2016, Taipei, Taiwan

"  Dedicated!Conference!on!Liquid!Biopsies!Asia!"  Key!Opinion!Leaders!(KOLs)!Akending!and!Presen?ng!"  Delegates!from!Across!Asia/Pacific!Region!"  Network!and!Engage!with!KOLs!–!All!Classes!of!Liquid!

Biopsies!Represented!"  Please!Scan!QR!Code!with!iPhone/iPad/Android!to!Navigate!

to!Conference!Website!with!All!Conference!Details!

GENReports: Market & Tech...

Documents

Transcript of GENReports: Market & Tech...