Comprehensive Characterization of Solid Tumor The right drug or right trial… 700 Ellicott Street | Buffalo NY, 14203 For Every Patient Booth 635 Immune Profiles for Precision Using Immune Report Card℠ Nesline 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 Institute2, Buffalo, NY # [email protected]; *[email protected]

Introduction Immune Response Markers Actionability

Amplified High High All tumor types Monoclonal antibodies directed at inhibitory immune High High

receptors have emerged as successful treatment ≥ 1% Moderate TGF1 options for numerous tumor types using both mono Infiltrating 8% Moderate ADORA2A and combination modalities. However, response rates Moderate 35% are low (20-30%) for current FDA approved checkpoint Not Amplified CSFR1 Stable 37% inhibitors, and better predictive markers are needed Low Non- Infiltrating IL10 to support patient selection for treatment. We < 1% Low GITR 20% present findings from patients tested by Immune Low Minimal VISTA to Absent Report Card℠, a validated NYS CLEP approved clinical IDO1 assay that measures markers of checkpoint inhibitor TIM3 PD-L1 PD-L1 PD-L1/L2 MUB MSI TILS TILS OX40 Response Marker Positive (FDA Tumor Type) response and targets in immunotherapeutic clinical IHC RNA-Seq Copy Quantity Pattern CD38 Response Marker Positive (Other Tumor Type) trials for appropriate treatment selection. Number LAG3 Overexpressed target in clinical trials CD40 No actionable immune marker ICOS • 160 (52%) patients harbor at least one response marker with CTLA4 TNF CCR2 CD27 77 (25%) having >1 response marker. CD137 Methods • 64/114 (56%) of PD-L1 IHC+ cases have >1 response marker On and off-label actionability across 30 tumor types • 43 (14%) are “hot” tumors with most cases (62%) in tumors with FDA approved checkpoint inhibitors Tumor types with FDA approved checkpoint inhibitors 306 FFPE samples in 30 solid tumor types (including

163 patients across 12 tumor types with FDA TGF1 approvals for checkpoint inhibitors) were Immunotherapeutic Trials 10% comprehensively evaluated by Immune Report Card ADORA2A Unique Unique 34% for markers of response to checkpoint inhibitors Target Therapies (Single and/or Combination) Trials Patients GITR 26% including: ADORA2A 3 97 AZD4635; CPI-444; PBF-509 ; BMS-813160; CCX872-B; PF- • PD-L1 pathway activation by IHC, RNA-Seq and copy CCR2 2 11 VISTA 04136309 TIM3 number/amplification CD137 6 50 ; Utomilumab 30% • Genomic instability using microsatellite instability CD27 1 24 CD38 CD38 3 62 Daratumumab CSF1R ADC-1013; APX005M; CP-870,893; RO7009789; (MSI) by PCR and mutational burden (MUB) by CD40 11 53 OX40 SEA-CD40 IL10 DNA-Seq. Cabiralizumab; Emactuzumab; AMG 820; BLZ945; >1 Response Marker Positive (PD-L1, TILS, MSI, MUB) CSF1R 13 113 IDO1 • Tumor infiltrating lymphocytes (TILS) expression by LY3022855; PD-0360324; PLX73086 ICOS PD-L1 IHC >=1% positive only ; ; AGEN1884; BMS- CTLA4 CTLA4 108 42 Overexpressed target in clinical trials IHC and quantity by RNA-Seq to characterize “hot” 986218; MK-1308 CD40 CCR2 No actionable immune marker BMS-986156; GWN 323; INCAGN01876; MEDI1873; LAG3 TNF (overexpression of CD8 and infiltrating or excluded GITR 7 82 CD27 MK-4166; TRX518 CD137 TILS pattern) and “cold” tumors ICOS 2 60 GSK3359609; JTX-2011 Epacadostat; Indoximod; BMS-986205; GDC-0919; IDO1 17 87 Clinical trials may be more appropriate for some patients • 20 therapeutic targets in clinical development. KHK2455; PF-06840003 IL10 1 64 MK-1966 eligible for checkpoint inhibitors. BI 754111; BMS-986016; LAG525; MGD013; MK- LAG3 11 53 4280; REGN3767; TSR-033 Workflow BMS-986178; GSK3174998; INCAGN01949; OX40 10 60 MEDI0562; MEDI6383; MEDI6469; MOXR0916; PF- Conclusions 04518600 1 Construct Library 2 Prepare Template 3 Run Sequence 4 Analyze Data ; ; AGEN2034; BGB-A317; As checkpoint inhibition moves from treatment of last PD-1 404 73 BI 754091; JNJ-63723283; MEDI0680; MGD013; resort to first and second line therapy, Immune Report Card PDR001; PF-06801591; REGN2810; TSR-042 • RNA panel for Immune • Ion Chef™ System • Ion S5 XL™ System • Analysis solution with provides actionable results for the total tumor immune Response analysis ; ; ; CA-170; CX- • 16 – 20 samples per Torrent Suite™ PD-L1 157 73 • DNA Panel for MuB (CCP) run Software 072; FAZ053; KN035; LY3300054 microenvironment, including: analysis • immuneResponseRNA TGFB1 2 122 ; NIS793 Frontline Response Markers for Checkpoint Inhibition: • RNA Panel for T-cell plugin TIM3 3 49 LY3321367; MBG453; TSR-022 repertoire (TCRB) analysis • MuB caller TNF 1 21 Certolizumab • On/Off-Label: PD-L1 IHC (22C3, 28-8, SP142), MSI, MUB VISTA (B7-H5) 2 67 CA-170 • Additional Evidence: PD-L1 RNA-Seq, PD-L1/L2 copy 48 hour turnaround time number, TILS pattern and expression (hot vs. cold tumors) • Ion Torrent™ platform workflow Arm-specific matching provides options for all Subsequent Therapy Planning : • Ion AmpliSeq™ chemistry patients who either do not have at least one known marker • Overexpressed immunotherapeutic targets for optimal • Minimum specimen requirements of response or who are seeking second line treatment selection of combination therapy in clinical trials SITC 2017 - P16 Copyright 2017 OmniSeq, Inc.