GENReports: Market & Tech Analysis

Transcription

1 GENReports: Market & Tech Analysis > Enal Razvi, Ph.D. Biotechnology Analyst, Managing Director Select Biosciences, Inc.

2 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., Why,Liquid,Biopsies?! 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!! MinimallyI Invasive!means!for!Harves?ng!Biomarkers!from!Pa?ents!for!Disease!Monitoring! MinimallyMInvasive,Means,for,HarvesAng,Biomarkers,from,PaAents,for,Disease,Monitoring,Over,Time,

3 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,

4 One!of!the!challenges!in!the!development!of!biofluid!biopsies! is!the! sample!prepara?on!on!the!frontiend!from!clinicallyi relevant!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,

5 Comparison,of,Various,Classes,of,CirculaAng,Biomarkers,visM àmvis,their,suitability,for,liquid,biopsy,development, Exosomes,, Microvesicles, CirculaAng, RNA, CTCs, CirculaAng,CellM Free,DNA, Tissue,Sample,[as,a, Benchmark], Sample!Availability! Throughout!the! Disease!Process! Sample!Stability! When!Maintained! Ex#Vivo#[ie.,!postI explant]# U?lity!for! Longitudinal! Disease!Monitoring! [ie.,!ability!to! harvest!samples! from!pa?ents!over!?me]! Clinical!U?lity!as!a! Biomarker! Suitable,for,Liquid, Biopsy, Development, Yes, Yes, Only,in,Late,Stages, Yes, Invasive,Procedures,for, Harvest, Stable, Stable, Unstable, Stable, Stable,when,processed,, Yes, Yes, Yes,with,caveats, [ie.,,late,stages, more,amenable], Not, Demonstrated, Not, Demonstrated, with,excepaons, Only,Demonstrated, in,specific,disease, Classes, Yes,with,caveats, [ie.,,late,stages, more,amenable], Not,Demonstrated, with,excepaons, Invasive,Procedures,for, Harvest, Yes, Yes, Yes, Yes, No, Yes,

6 Various,Sources,of,CirculaAng,Biomarkers:, Analytes,for,Liquid,Biopsies! Circulating tumor cells (CTCs) Lysis Placental, fetal cells (utilized in NIPT) Necrosis Apoptosis Activated lymphocytes and other nucleated cells Source:!Pamela!Pinzani,!Univesità degli Studi di Firenze.!

7 Classes,of,Extracellular,Vesicles,(EVs):,PotenAal, for,liquid,biopsy,development, EV,Size,DistribuAon,May,Reflect,FuncAonal,Significance, " 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,

8 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,

9 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,, Source:,Luis,Diaz,et#al.,,

10 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 " Appropriate samples that are indicative of disease " Robust assays/approaches to characterize the circulating biomarkers in the liquid biopsy samples " Identifying those that are the most relevant with prognostic and/or predictive value " Minimally-invasive diagnostics development " Samples are reflective of the in vivo situation in the patient as opposed to a segment of the tumor " Longitudinal analyses of patient response to therapies [such as cancer therapeutics] without the need for costly, painful invasive procedures " Acceleration of adoption of precision medicine " Demonstration of clinical " Tissue Specificity of Origin of relevance for prognosis in the Disease can be Studied absence of large, multi-year prospective clinical trials of patient survival

11 Liquid,Biopsies,will,Move,to,the,PointMofM Care,(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! smartphonei based! 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!

12 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!

13 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!

14 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!