Comprehensive Characterization of Solid Tumor …

1 WorkflowNesline M1,#, Conroy J1,2, Pabla, S1, He J1, Burgher B1, Giamo V1, Andreas J1, DePietro P1, Papanicolau-Sengos A1, Gardner M1, Glenn S1,2, Morrison CM1,2,*OmniSeq, Inc1, Buffalo, NY; Roswell Park Cancer Institute2, Buffalo, NY # 2017 -P16 Comprehensive Characterization of Solid Tumor Immune Profiles for Precision Immunotherapy Using Immune Report Card 700 Ellicott Street | Buffalo NY, 14203 Booth 635 MethodsIntroductionConclusionsImmune Response MarkersImmunotherapeutic TrialsActionabilityArm-specificclinicalt rialmatchingprovidesoptionsforallpatient swhoeitherdonothaveatleastoneknownmarker ofresponseorwhoareseekingsecondlinetreat mentTargetUnique TrialsUnique PatientsTherapies (Single and/or Combination)ADORA2A397 AZD4635; CPI-444; PBF-509 CCR2211 Plozalizumab; BMS-813160; CCX872-B; PF-04136309CD137650 Urelumab; UtomilumabCD27124 VarlilumabCD38362 DaratumumabCD401153 ADC-1013.

2 APX005M; CP-870,893; RO7009789; SEA-CD40 CSF1R13113 Cabiralizumab; Emactuzumab; AMG 820; BLZ945; LY3022855; PD-0360324; PLX73086 CTLA410842 Ipilimumab; Tremelimumab; AGEN1884; BMS-986218; MK-1308 GITR782 BMS-986156; GWN 323; INCAGN01876; MEDI1873; MK-4166; TRX518 ICOS260 GSK3359609; JTX-2011 IDO11787 Epacadostat; Indoximod; BMS-986205; GDC-0919; KHK2455; PF-06840003IL10164MK-1966 LAG31153BI 754111; BMS-986016; LAG525; MGD013; MK-4280; REGN3767; TSR-033OX401060 BMS-986178; GSK3174998; INCAGN01949; MEDI0562; MEDI6383; MEDI6469; MOXR0916; PF-04518600PD-140473 Nivolumab; Pembrolizumab; AGEN2034; BGB-A317; BI 754091; JNJ-63723283; MEDI0680; MGD013; PDR001; PF-06801591; REGN2810; TSR-042PD-L115773 Atezolizumab; Avelumab; Durvalumab; CA-170; CX-072; FAZ053; KN035; LY3300054 TGFB12122 Fresolimumab; NIS793 TIM3349LY3321367; MBG453; TSR-022 TNF121 CertolizumabVISTA (B7-H5)267CA-170 160 (52%) patients harbor at least one response marker with 77 (25%) having >1 response marker.

3 64/114 (56%) of PD-L1 IHC+ cases have >1 response marker 43 (14%) are hot tumors with most cases (62%) in tumors with FDA approved checkpoint inhibitors< 1% 1%HighLowModerateAmplifiedNot AmplifiedHighLowModerateHighStableHighLo wModerateMinimal to AbsentNon-InfiltratingInfiltratingPD-L1 IHCPD-L1/L2 CopyNumberPD-L1 RNA-SeqMUBMSITILSQ uantityTILSP attern306 FFPE samplesin30solidtumortypes(including163p atientsacross12tumortypeswithFDAapproval sforcheckpointinhibitors)werecomprehensi velyevaluatedbyImmuneReportCardformarker sofresponsetocheckpointinhibitorsincludi ng: PD-L1pathwayactivationbyIHC,RNA-Seqandco pynumber/amplification Genomicinstabilityusingmicrosatelliteins tability(MSI)byPCRandmutationalburden(MU B)byDNA-Seq.

4 Tumorinfiltratinglymphocytes(TILS)expres sionbyIHCandquantitybyRNA-Seqtocharacter ize hot (overexpressionofCD8andinfiltratingorexc ludedTILS pattern)and cold tumors ,responseratesarelow(20-30%)forcurrentFD Aapprovedcheckpointinhibitors, , Marker Positive (FDA Tumor Type)Response Marker Positive (Other Tumor Type)Overexpressed target in clinical trialsNo actionable immune markerTumor types with FDA approved checkpoint inhibitorsAll Tumor types34%30%26%10%>1 Response Marker Positive (PD-L1, TILS, MSI, MUB)

5 PD-L1 IHC >=1% positive onlyOverexpressed target in clinical trialsNo actionable immune markerOn and off-label actionability across 30 Tumor typesClinical trials may be more appropriate for some patients eligible for checkpoint 1 ADORA2 ACSFR1 GITRVISTAIDO1 TIM3OX40CD38 LAG3CD40 ICOSCTLA4 CCR2CD137 TNFCD27IL10 TGF 1 ADORA2 AGITRTIM3CD38 CSF1 ROX40IL10 IDO1 ICOSCCR2 CTLA4 LAG3 VISTACD137 TNFCD27CD40 Copyright 2017 OmniSeq, ,ImmuneReportCardprovidesactionableresul tsforthetotaltumorimmunemicroenvironment ,including:FrontlineResponseMarkersforCh eckpointInhibition: On/Off-Label:PD-L1 IHC(22C3,28-8,SP142),MSI,MUB AdditionalEvidence:PD-L1 RNA-Seq,PD-L1/L2copynumber,TILS patternandexpression( )SubsequentTherapyPlanning.

6 Overexpressedimmunotherapeutictargetsfor optimalselectionofcombinationtherapyincl inicaltrials Ion Torrent platform workflow Ion AmpliSeq chemistry Minimum specimen requirementsConstruct Library1 Prepare Template2 Run Sequence3 Analyze Data4 RNA panel for Immune Response analysis DNA Panel for MuB (CCP) analysis RNA Panel for T-cell repertoire (TCRB) analysis Ion Chef System Ion S5 XL System 16 20 samples per run Analysis solution with Torrent Suite Software immuneResponseRNA plugin MuB caller48 hour turnaround timeThe right drug or right Every Patient