IT SAR* Targeted with a mAb Alternatively spliced extradomain-B of fibronectin Philogen (Fibromun/L19-TNF) •• TNFα *Soft Tissue Sarcoma Clinical stage codes M MEL › Toxic to tumor neovasculature and activates the endothelium; highly toxic if used systemically Preclinical/Discovery OTC Over-the-Counter Not targeted with a mAb Boehringer Ingelheim (Beromun; isolated limb perfusion) M SAR • Phase 1 NDA New Drug Application Beromun Limited to use in isolated limb perfusion •• Phase 2 BLA Biologics License Application ••• Phase 3 MAA Marketing Authorization Application (Europe's NDA) Long-acting SC Merck (Sylatron/peginterferon α-2b) M MEL Class has M Marketed D Dormant/discontinued Less frequent injections Ñ february 2017 known G Generic Failed survival IB FKD Therapies Oy (Instiladrin/rAdIFN w/ Syn3) •• UCC RCT Randomized Controlled Trial CP Compounding Pharmacy benefit Interferon-α (IFNα) Genetically modified non-replicating to the tumor Adenovirus expressing IFNα2b IST Investigator-Sponsored Trial PD(L)1 immuno-oncology 21 22 M NHL PDUFA PDUFA POC: Unknown • Enhances T-cell and DC response via a poorly-characterized MoA M MEL • Associated with dose-limiting AEs, including influenza-like symptoms (fatigue, fever, headache and muscle SC/IM/IC Merck (Intron-A/interferon α-2b) M CLL ANDA Abbreviated New Drug Application POC: Validated aches), nausea, dizziness, anorexia, depression and leukopenia Merck (SC Intron-A/interferon α-2b + IV Keytruda/) MEL FAILED OL Off-label POC: Failed IFNα2b Roche (IV Tecentriq/ + SC interferon-α2b) • Inton-A Short-acting more frequent M NHL Routes of delivery injections M MEL IV Intravenous IB Intravesical/Intrabladder CLL MDS SC Roche (recombinant interferon alfa-2a (Roferon-A)) M •• Innate Pharma/Bristol-Myers Squibb Provide IFNα2a ID Intradermal IC Intracerebral ST • (lirilumab IV+ Opdivo/ IV) Unknown Multikine mixture IT/SC CEL-SCI (Multikine) ••• HNC RCT:YE17 IM Intramuscular EC Epicutaneous RCT:2H16 AML •• broadly-acting survival Proprietary mix of 19 , and other molecules (no , not a vaccine). PDAC RCT:YE16 SC Subcutaneous IN Intranasal MM •• Anti-KIR mAbs •• •• GBM RCT:MY16 PO Oral Dosage AML •• KIR is an inhibitory on NK cells that binds HLA-C on tumor cells cytokines benefit Multikine: YE17 CRC CLL •• Innate Pharma/Bristol-Myers Squibb (lirilumab) IV Poorly-defined MOA •• IVT Intravitreal QD Once a day •• PC Intrathercal Intrathecal BID Twice a day HNC PO Eli Lilly (LY2157299/galunisertib) + IV Bristol-Myers Squibb (Opdivo/nivolumab) •• OC •/•• IT Intratumoral TID Three times a day OC •/•• PO Eli Lilly (LY2157299/galunisertib) • ST TD Transdermal QW Once a week CLL •/•• Innate Pharma/AstraZeneca (IPH2201) IV Anti-NKG2A mAbs TGFβ kinase inhibitor MedPacto (TEW-7197) • ST Disinhibit NK cells Bristol-Myers Squibb/Rigel  IPL Intrapleural Q2W Once every 2 weeks NKG2A is an inhibitory receptor on NK cells and some CD8+ T cells that binds overexpressed HLA-E on tumor cells. The Cheot Poteta Cae The Cheot Scholar Rock/Janssen  IP Intraperitoneal QM Once a month lirilumab+pembrolizumab 3Q18 hto  Anti-TGFβ mAb Novartis (Xoma-089) ••• MEL RCT:MY18 hto aet 22 aet 21 2 othea aet Incyte (INCB24360/epacadostat) PO + Merck (Keytruda/pembrolizumab) IV •/•• ST ArGEN-X (ARGX-115)  •• ST  Innate Pharma (IPH4031) Anti-MICA/MICB mAbs 22 Inhibit TGFβ pathway Anti-GARP mAb - inhibitor of TGFβ release Incyte (INCB24360/epacadostat/INCB24360) PO •• MDS MICA/B overexpression on tumor cells disrupts costimulatory signaling through NKG2D on NK cells and some T cells. • Enhances tumor growth, promotes formation of tumor stroma, and increases metastatic potential AML • Glycostem Therapeutics (oNKord) IV  +Bristol-Myers Squibb (Opdivo/nivolumab) IV •/•• OC • TGFβ acts as a tumor growth suppressor during early tumorigenesis. Huabo Biopharm (HB-002)  Celgene TGFβ- and VEGF-targeting bifunctional fusion Incyte (INCB24360/epacadostat) PO + Roche (Tecentriq/atezolizumab) IV • NSCLC  Fate Therapeutics Derived from stem cells • Suppresses Treg activity •• OC   Ziopharm Isarna (Trabedersen) IV •• CC galunisertib: MY18 TGFβ2 antisense  Nantkwest (haNK) IV High-affinity binding to Off-the-shelf human NK cell line •• MDS ST Added synergy with mAbs such as Rituxin or Herceptin Incyte (INCB24360/epacadostat) PO •/•• Tilos Therapeutics   MCC •• Irradiated cell line TGFβ pathway inhibition with mAb against latency iTeos Therapeutics/  AML • Nantkwest (aNK/NK-92) IV associated peptides ioMET Pharma/Merck No added specificity Not -specific RedX Oncology  Fortress Bio Bristol-Myers Squibb/Flexus  AML •/•• (CNDO-109-activated allogeneic NK cells) IV Provide NK cells / / IDO Nektar (NKTR-218)  Can be manufactured at central facility Expressed by tumor cells and APC 1 1 2 Ensemble Therapeutics  AML •/•• University of Texas M.D. Anderson Cancer Center IV aNK:YE16 Patient-specific manufacturing /1 /1  Ex vivo IL-21-activated allogeneic NK cells Pfizer/iTeos Therapeutics 3 1 11 ioMET Pharma  Must be manufactured in-house TDO  SMM •• University of Arkansas/Millenium IV See ‘T-cell Growth Factors’ NK-cell growth factors /1 /1 RedX Oncology Ex vivo-expanded autologous NK cells 1 23 22 Inhibit IDO) and/or TDO • Upregulated in hepatocytes and in the brain • Potential for on-target toxicity Bristol-Myers Squibb/Flexus  /1 ioMET Pharma  IDO and TDO deplete tryptophan. Low tryptophan levels promote Treg differentiation and suppress DC function, which dampen the immune response. 2 11 RedX Oncology  See Immuno-Oncology: CAR-T Bristol-Myers Squibb/Flexus  Antigen-specific epacadostat+pembrolizumab: MY18 Dual IDO/TDO /1 Roche/Curadev (RG70099)  1 PO NewLink Genetics (NLG8189/indoximod) •/•• Shielded from Unknown target in IDO/TDO pathway ST •/•• Nektar (NKTR-214) IV Reduced IL-2Rα binding Selective for effector T cells over 2  PEGylation enhances tumor targeting activating T cells in Target other components of the IDO/TDO pathway KYN Therapeutics Allows for receptor recycling regulatory T cells Signal NK Cell Tumor Cells Regulatory Kynurenine peripheral blood •/•• BC Eliminate Siglec family Sialyated glycan PD1 CD27 •/•• NSCLC ST • Roche (RO6874281) IV Broad range PO Incyte (Jakafi/Ruxolitinib) • ST Anti-fibroblast activation protein (FAP) fusion Antibody capillary leak PDAC Antigen target is expressed in wide range of tumor types Reduced IL- KIR MHC Class I CTLA4 Neurophil •• targeting to Selective for syndrome, JAK1/2 PO NSCLC 2Rα binding Inhibitory Inhibit Janus kinase (JAK) Gilead (Momelotinib) • effector T cells over more CD96 TNFRSF25 VEGF tumor Allows for receptor Signal Decrease inflammatory cytokines that recruit MDSCs Incyte (INCB-39110) •/•• ST ST • IV CD155 Roche (RO6895882) Narrow range Localization may still be recycling regulatory T cells convenient JAK1 Anti- (CEA) antibody fusion TIGIT •• PDAC RCT:MY17 •• HNC RCT:3Q17 Antigen target is expressed in subset of tumor types driven by IL-2 binding GITR LAG3 dosing UCC RCT:MY17 OC RCT:YE17 DIS- •• •• CONTINUED Merck KGaA (Selectikine/EMD 521873) IV Not shielded from MICA family 4-1BB ICOS NSCLC RCT:YE17 Anti-DNA antibody Stimulatory NKGR2 •• activating T cells in Signal PO Acerta Therapeutics (ACP196/acalabrutinib) + IV Merck (Keytruda/pembrolizumab) •/•• GBM RAET1/ULBP family OX40 CD25 MEL •• Philogen (Darleukin/L19-IL-2) IV Broad range peripheral blood Second-generation BTK inhibitor REDX Oncology  Alternatively spliced extra-domain B (EDB) of fibronectin IL-2  Antigen target is expressed in wide range of tumor types Potential for better safety profile (lower infection risk, bleeding risk, and GI tox) due to improved specificity Advinus Therapeutics MCC •• • Canonical T cell growth factor AML Inhibit Bruton’s tyrosine kinase (BTK) M MCL • Philogen (Teleukin/F16-IL2) IV IL-2 fused • Induces activation and proliferation of NK cells, B Target myeloid-derived suppressor cells (MDSCs) ECM tenascin-C Not selective for Targeting BTK inhibits MDSC migration into tissues and expression of suppressive factors such as nitric oxide (NO) as well as Tregs PO AbbVie/JNJ (Imbruvica/ibrutinib) M CLL cells and monocytes to targeting MDSCs are immature myeloid cells that maintain the immunosuppressive tumor microenvironment via the production of arginase, IDO, ROS and suppressive cytokines. First-generation BTK inhibitor •/•• ST NHL •/•• Alopexx (DI-Leu16-IL2) IV effector T cells PO IV PDAC Anti-CD20 antibody molecule Proleukin • Selectivity problems associated with: • BTK: infection risk | EGFR: GI tox, and rash | JAK3: bleeding AbbVie/JNJ (Imbruvica/ibrutinib) + AstraZeneca (MEDI-4736/) •/•• MEL •/•• acalabrutinib+Keytruda: MY17 UCC •/•• Narrow range AstraZeneca (PO AZD5069 + IV durvalumab) •/•• PDAC MM •/•• IV Antigen target is expressed in subset of tumor types Class has confirmed overall CXCR2 PO AstraZeneca (AZD5069) •/•• HNC Altor Bioscience (ALT-801) p53-specific single chain TCR NK RCC M survival benefit and has Inhibit IL-8/IL-8RB (CXCR2) signaling IV Bristol-Myers Squibb (Humax-IL-8) •/•• ST MEL •• Nestle Health Science (Proleukin/aldesleukin) IV Paracrine signaling by tumor-derived IL-8 to CXCR1 and CXCR2 promotes the trafficking of neutrophils and MDSCs into the tumor microenvironment. IL-8 also has a role in the development IL-8 Associated with capillary leak syndrome, must be dosed in specialized setting induced long-term cures of cancer stem cells. PO Dompe (Reparixin) •• BC MEL •• Lion (LN-144) IV CXCR2 and IL-8 Tumors are surgically removed, tumor infiltrating leukocytes are isolated and expanded in a central facility, and re-infused into patients IV Takeda (TAK-202/) + IV Bristol-Myers Squibb (Opdivo/nivolumab) • MEL PO Pfizer(PF-04136309) •/•• PDAC Ex vivo T cell growth factors Inhibit CCR2 Promote differentiation of MDSC into mature, non-suppressive cells EBV CTL •• Cell Medica (CMD003) IV PO ChemoCentryx (CCX872) •b PDAC Pre-existing Epstein-Barr virus-specific T cells are expanded ex vivo from peripheral blood Requires complicated patient specific manufacturing Activate NK Cells Reverse the Dana Farber Cancer Institute (Biological:  NASO •• Inhibit polyamide synthesis and uptake PO Aminex (AMX-513) Epstein-Barr Virus Specific Immunotherapy)IV LN-144 Peripheral PBMCs are infected with EBV and subsequently irradiated to develop autologous EBV-specific T cells The presence of polyamines such as IDO, arginase, and adenosine promotes the presence of MDSC as well as Tregs PO Corvus (CPI-444) + IV Roche (Tecentriq/atezolizumab) • ST  Nektar (NKTR-255) Treg PEGylation enhances half life Suppressive PO Corvus (CPI-444) • ST PO Novartis (PBF-509) • NSCLC   Kadmon (KD033) IL-15 Antagonize adenosine A2A receptor AstraZeneca/Heptares Targeted with PDL1 mAb • Canonical NK cell growth factor • The receptor IL-15Rα can be presented in trans on an APC or in cis on an NK or T cell  Microenvironment • Elevated cAMP blunts TCR-mediated cytotoxicity • Inhibits effector T cells • Expands Treg cells • Enhances NK cell cytotoxicity Domain Therapeutics ST • NCI (rIL-15) I IV • Induces activation and promotion of T cells, which are then biased towards a memory phenotype • IL-15Rα complexes with the β and γ chain of IL-2R to signal PO Kyowa Hakko Kirin (istradefylline) *  Oxis Biotech (OXS-3550) rIL-15 PO Juno Therapeutics/RedoxTherapies (V2006/vipadenant)   Armo (AM0015) Inhibit adenosine signaling *Marketed Parkinsons in Japan Has a short half-life and dosing issues rIL-15:YE16 NK Adenosine promotes differentiation of immunoinhibitory Tregs IV AstraZeneca (MEDI-9447) • ST Corvus   NeoImmuneTech (NIT-02) IV CD73 antagonist Fc fusion Decrease adenosine production via the Juno Therapeutics/RedoxTherapies  Longer acting and better manufacturing yield IL-7 Target immunosuppressive function of Tregs ectonucleotidases CD39 and CD73 Innate Pharma/Orega Biotech  • Augments antigen-specific T cell responses, selectively expanding CTL over Tregs • Maintains a stable pool of naive and memory T cells NK CD39 antagonist Provide T-cell growth CPI-444: MY18 Block IL-35 Tizona Therapeutics  RCT:YE16 PC •• NCI (CYT107) IV • Promotes differentiation of B cells • Signals through the IL-7R complexed with the γ subunit of the IL-2R NK Recombinant protein Tregs secrete IL-35, which promotes Treg proliferation factors Novartis/Surface Oncology  CYT107: 1Q17 Signals through IL-2Rγ Myeloid-  Piper Therapeutics DIS- Bristol-Myers Squibb Unspecified targets within the CONTINUED MEL •• Shares part of signaling pathway with validated IL-2 (recombinant IL-21/denenicokin) SC/IV Trillium Therapeutics (TTI-621) • SHT DIS- Bristol-Myers Squibb (recombinant IL-21/ IL-21 SIRPα-Fc fusion protein CONTINUED tumor microenvironment denenicokin IV) + (Opdivo/nivolumab IV) • Activates T cells, particularly along the Th17 and Treg • Can induce proliferation and activation of CD8 cells, but • Promotes antigen-specific responses and differentiation • Has failed as monotherapy • Decoy receptor that blocks CD47 signaling • Lower affinity for RBCs; could have less severe hematological toxicity IV Forty Seven (Hu5F9-G4) • ST axis by binding IL-21R, which complexes with the γ along a less-activated pathway than IL-2, IL-15, or IL-7 into plasma cells in B cells derived  ST Altor Bioscience (ALT-803) ISC/V + Vasculox NSCLC ••/• subunit of IL-2R Bristol-Myers Squibb (Opdivo/nivolumab) IV Celgene (CC-90002)  HM UBC ••/• Monospecific antibody Alexo  FAILED NHL ••/• Supressor Anti-CD47 mAb Tioma  MEL ••/• Superagonist of IL-15 bound to IL-15Rα-Fc fusion Higher affinity for RBCs; could have more severe hematological toxicity Bispecific (CD47xCD19) antibody NovImmune (NI-1701)  HM MM ••/• Increased serum half-life CD19 expressed on B cells •• PVNS RCT:4Q17 PDAC Target SIRPα/CD47 ••/• RCT:MY18 CD47 on tumor cells bind to SIRPα on to prevent phagocytosis IV Novartis (MCS-110) •• BC HT • Altor Bioscience (ALT-803) ISC/V Cell IV Roche (Emactuzumab/RG-7155 + Tecentriq/Atezolizumab) • ST Signals through IL-2Rγ and IL-2Rβ with no α subunit targeting Alexo  ST • Alkermes (ALKS 4230) IV IV Roche (Emactuzumab/RG-7155) •/•• PVNS Fusion protein of IL-2 and IL-2Rα Unknown phenotype, likely similar to IL-2 and IL-15 TTI-621: YE16 High-affinity soluble SIRPα monomers IV Five Prime Therapeutics (FPA-008) + IV Bristol-Myers Squibb (Opdivo/nivolumab) •/•• ST • Novartis (het IL-15) SC IV Five Prime Therapeutics (FPA-008) •/•• PVNS ALT-803+Opdivo: YE18 mAbs ST IL-15/IL-15Rα fusion • Dosed IV • More specific for CSF1R (AMG-820) + IV Merck (Keytruda/pembrolizumab) • Amgen (AMG-820) • ST Signal CTL Tumor Cells IV Eli Lilly (IMCCS4) • ST Class has unknown overall Trillium Therapeutics (CD200Fc)  IV  OncoSec (OMSI100) + Target CD200/CD200R Transgene (TG3003) MEL •• survival benefit PDL1 PD1 Merck (Keytruda/pembrolizumab) IT/IV Tumor expressed CD200 prevents activation ••• PVNS RCT:1Q18 MEL •• PDL2 CD80 •• GBM MCC •• •• BC HNC •• Electroporation delivery B7-H3 ? Tyrosine kinase inhibitor PO Daiichi Sankyo (Pexidartinib/PLX-3397) •/•• AML CTL •• PO Daiichi Sankyo (Pexidartinib/PLX-3397) + IV Merck (Keytruda/pembrolizumab) •/•• MEL Inhibit colony-stimulating factor 1 receptor (CSF1R) inhibitor • Dosed orally ?  BC • OncoSec (OMSI100) IT Inhibitory B7-H4 kill M2 macrophages depend on CSF1R signaling for survival PO Deciphera (DCC-3014) APC • Associated with off-target effects including inhibiting the oncogene c-KIT PO Daiichi Sankyo (AC708)  BC •• Signal Butyrophilin family ? GBM • Ziopharm (Ad-RTS IL-12) IT Non-replicating adenovirus Genetically-engineered vector IL-12 production activated by oral veledimex Inhibit RON PO Bristol-Myers Squibb/Aslan (ASLAN002) ••* GASTRIC OC •• CD155 TIGIT • Expressed on myeloid cells • Decreases production of IL-12, IFNγ and TNF, and increases IL-10 IL-12 *In Asia GBM  Celsion (GEN-1) IP Treg Tumor Cells • Tumors secrete RON’s ligand, macrophage stimulating protein (MSP) • Promotes M2 phenotype Peregrine Pharmaceuticals (bavituximab) + IV AstraZeneca (MEDI-4736/durvalumab) •/•• ST PEG-polyethylenimine-cholesterol lipopolymer carrier • Enhances antigen specific response • Activates and induces proliferation of CD8+ T cells and NK cells. Galectin 9 TIM3 •/•• MEL HCC • • Produced mainly by phagocytic cells in response to antigenic • Promotes CD4+ T cell differentiation into Th1 Phosphatidylserine CD8+ •/•• HCC RCC • Immunicum (COMBIGDC) IT stimulation Allogenic dendritic cells that release cytokines Target phosphatidylserine • CRC ¨ *DIS- OMSI100: MY18 Drive M2 M1 macrophage differentiation Drives differentiation of M2 macrophages and production of immunoinhibitory cytokines NSCLC CONTINUED No genetic engineering Does not signal through IL-2R Disinhibit APCs *DIS- ST • Merck KGaA (NHS-IL12) SC BC CONTINUED emactuzumab+Tecentriq: 3Q18 *DIS- Recombinant protein IV Peregrine Pharmaceuticals (bavituximab) PDAC CONTINUED ID *Suspended ST Armo Biosciences (AM0010/pegylated IL10) + •/•• IV help Merck (Keytruda/pembrolizumab) IL-10 Inhibit phosphoinositide 3-kinase γ (PI3Kγ) IV Infinity Pharmaceuticals(IPI-549) PO + Merck (Keytruda/pembrolizumab) • ST ST •/•• Armo Biosciences (AM0010/pegylated IL10) ID PO ST • Usually thought to be immunosuppressive Blocks macrophage differentiation and myeloid cell migration Infinity Pharmaceuticals (IPI-549) •  Merck (MK1966) CD4+ • Induces Treg differentiation and inhibits macrophages and dendritic cells but can activate in some cases by inducing T cell activation, clonal response, and tumor infiltration  Drive M2 macrophages to apoptosis Anti-CD206 mAb conjugated to a cytotoxic payload Macrophage Therapeutics AM0010: YE16

MEL M RCT:3Q20 UCC ••• Activate immune IB BDI Pharma/Sanofi Aventis (TheraCys) M UCC Deliver mycobacteria to tumor Attenuated bacillus Calmette-Guerin/BCG NSCLC M CRC ••• Cancer Abbreviations Immuno-Oncology Abbreviations RCT:1Q19 Class has response with RCC M PDAC ••  Evelo 4-1BB/CD137 TNF receptor superfamily member 9 LTA lymphotoxin-α HL M NHL •• proven microbesm Hematological Tumors Solid Tumors CD4+ Undisclosed mechanism Vedanta  HNC M OC •/•• Re-direct T-cell targeting Likely activates the immune system through BTLA B and T lymphocyte attenuator MIC MHC class I polypeptide-related sequence See Immuno-Oncology: CAR-T Activate T-Cell survival Hypothesized synergy with PD1 ALL Acute Lymphoblastic Leukemia AC Anal Cancer RCT:2Q17 GBM BC TLR stimulation among other pathways BTNL2 butyrophilin-like protein 2 MICA MHC class I polypeptide-related sequence A ••• • benefit •/•• NSCLC AML Acute Myeloid Leukemia BCC Basal Cell Carcinoma RCT:3Q17 SCLC ••• PC • via genetic engineering IV Biothera (Imprime PGG) •/•• CRC BTK Bruton’s tyrosine kinase MICA/MICB MHC class I polypeptide-related sequence A/B TheraCys ASM Aggressive Systematic Mastocytosis BC Breast Cancer RCT:MY19 HCC ••• GASTRIC • Provide S. cerevisiae polysaccharide CEACAM1 Carcinoembryonic antigen-related cell adhesion molecule 1 NK Natural killler Response IV/IT Janssen/Alligator Bioscience (ADC-1013) • ST CEL Chronic Eosinophillic Leukemia BT Biliary Tract RCT:3Q19 ESO ••• Bristol-Myers Squibb (Opdivo/nivolumab) IV IV Roche (RG7876+Tecentriq/atezolizumab) • ST CSF1R colony-stimulating factor 1r NKG2A Killer cell lectin-like receptor subfamily C member 1 MEL M RCT:YE17 OC •• CLL Chronic Lymphocytic Leukemia CC Cervical Cancer Roche (RG7876) • ST CTLA4 Cytotoxic T lymphocyte associated protein 4 OX40/CD134 Tumor necrosis factor (TNF) receptor superfamily member 4 NSCLC M MCC •• CML Chronic Myeloid Leukemia CIN Cervical Intraepithelial Neoplasia IV Apexigen (APX005M) + IV Merck (Keytruda/pembrolilzumab) • ST CXCL12 (C-X-C motif) ligand 12 PBMC Peripheral blood mononuclear cell HNC M BT •• IV Apexigen (APX005M) • ST CTCL Cutaneous T-Cell Lymphoma CHOR Chordoma RCT:3Q20 UCC ••• SAR •• CXCR4 C-X-C chemokine receptor type 4 PD1 Programmed cell death 1 IV Genetics (SEACD40) • ST DLBCL Diffuse Large B Cell Lymphoma CRC Colorectal Cancer RCT:3Q17 BC ••• RCT:1Q18 NHL •/•• mAbs FAET1/ULBP retinoic acid early transcripts 1/UL16‑binding protein PDL1/2 PD1 ligand 1/2 IV Cancer Research UK (Chi Lob 4/7) • ST RCT:1Q18 GASTRIC ••• RCT:2Q21 RCC •/•• FL Follicular Lymphoma DFSP Dermatofibrosarcomic Protuberans GARP leucine-rich repeat containing 32 PVR poliovirus receptor Bristol-Myers Squibb  RCT:1Q18 HL ••• PC •/•• Monospecific mAb HES Hypereosinophillic Syndrome EC Esophageal Cancer GITR/TNFRSF18 Glucocorticoid-induced TNF receptor-related protein RON Recepteur d’Origine Nantais Target CD40  RCT:3Q18 MM CLL/SLL Activate Celldex (CD40 agonist antibody) ••• •/•• CD8+ HCL Hairy Cell Leukemia FTC Fallopian Tube Cancer granulocyte–macrophage colony-stimulating factor Solid and Hematological Tumors DIS- GM-CSF SHT • Expressed on activated APCs and B cells • Promotes antigen-specific T cell response IT Pfizer (CP-870893) • ST CONTINUED RCT:MY18 ESO ••• SCLC • HL Hodgkin Lymphoma GEJ Gastric or Gastro Esophageal Junction Cancer HHLA2 HERV-H LTR-associating protein 2 Siglec sialic acid-binding immunoglobulin-type lectin RCT:1Q19 HCC ••• MES • ADC-1013:3Q17 Multimeric Biotherapeutics  HT Hematological Tumors SIRPα signal-regulatory protein RCT:3Q19 CRC MCL Mantle Cell Leukemia GIST Gastrointestinal Stromal Tumor ••• AC •  Formulated CD40L Apogenix GmbH (APG-1232) HVEM herpes virus entry mediator ST Solid Tumors DLBCL ••• Merck (Keytruda/pembrolizumab) IV CD8+ MLL-r Rearranged Mixed Lineage Leukemia GASTRIC Gastric Cancer SCC •• MM Multiple Myeloma GLI Glioma ICOS Inducible T cell co-stimulator STING transmembrane protein 173 SHT IT ST ICOSL inducible T cell co-stimulator ligand TGFβ transforming growth factor-β • Regeneron/Sanofi(REGN2810) IV Immune STING agonists Novartis/Aduro Biotech (ADU-S100) • MDS Myelodysplastic Syndrome HNC Head and Neck Cancer  ST •/•• Incyte/Jiangsu Hengrui Medicine (SHR-1210) • Induces IFN-β production which primes T cells • Drives abscopal response in preclinical studies IFM Therapeutics IDO/TDO Indoleamine 2,3-dioxygenas / Tryptophan 2,3-dioxygenase TIGIT T cell immunoreceptor with Ig and ITIM domains NMC NUT-Midline Carcinoma HCC Hepatocellular Carcinoma ST • AstraZeneca (MEDI0680) IV IFN Interferon TIM3 T cell immunoglobulin and mucin domain 3 ST • IV WM Waldenstrom Macroglobulinemia HPV Human Papilloma Virus associated Cancers Pfizer (PF-06801591) RIG-I agonist IT Rigontec GmbH (ImOI100)  IFNγ interferon-γ TL1A TNF-like ligand 1A ST • BeiGene (BGB-A317) IV Amplify NMC NUT-Midline Carcinoma LC Lung Cancer • Expressed ubiquitously • Induces IFN-β production which primes T cells IgSF immunoglobulin superfamily TMIGD1/2 transmembrane and immunoglobulin domain-containing protein 1/2 ST • Tesaro (TSR-042) IV WM Waldenstrom Macroglobulinemia MA Malignant Ascites ILT immunoglobulin-like transcript TNFR TNF receptor ST • Sorrento Therapeutics/Servier (STI-A1110) existing APC Response iNHL Indolent Non-Hodgkin’s Lymphoma MEL Melanoma IM GSK (monophosphoryl lipid A (MPL) in Cervarix vaccine) M CC ITK IL2-inducible T-cell kinase TNFRSF25/DR3 TNF receptor superfamily member 25 ST • TLR2 and TLR4 response IM GSK (SB-AS02B adjuvant) •• MEL NHL Non-Hodgkin Lymphoma MCC Merkel Cell Carcinoma JAK Janus Kinase TNFα tumour necrosis factor-α. CRC • GSK/AstraZeneca (AMP-224) IV/IV Expressed predominately on monocytic cells Blocking PDL2-Fc fusion protein PD1 Mature NMC NUT-Midline Carcinoma MES Mesothelioma KIR Killer cell immunoglobulin-like receptor VEGF vascular endothelial growth factor UCC M MEL • Target pattern WM Waldenstrom Macroglobulinemia MTC Medullary Thyroid Carcinoma LAG3 Lymphocyte-activation 3 NSCLC M OC • VISTA V-region immunoglobulin-containing suppressor of T cell activation IM GSK (SB-AS15 adjuvant) •• MEL iNHL Indolent Non-Hodgkin’s Lymphoma NASO Nasopharyngeal RCT:2H16 RCC ••• MM • recognition receptors TLR4 and TLR9 LIR leukocyte immunoglobulin-like CD4+ Recognize pathogen and damage-associated Expressed predominately on monocytes, mature macrophages and dendritic cells RCT:YE16 BC ••• NHL • Against Dendritic molecular patterns and activate a response RCT:2Q19 CRC ••• MDS • RCT:MY19 SAR •• AML • PD1 and PDL1/2-targeted agents TLR4 ADU-S100: MY17 Systemic IM/IT Immune Design (IDC-G305/GLAAS) • HT DLBCL •/•• Roche (Tecentriq/atezolizumab) IV • PD1 is expressed on T cells while its ligands, PDL1/2 are expressed on tumor cells. • Targeting the PD1/PDL1 axis has higher safety and efficacy than targeting CTLA4. Expressed predominately on monocytes, mature macrophages and dendritic cells, mast cells PDUFA:2Q17 NSCLC ••• RCT:4Q17 GASTRIC •/•• Cell administration and the intestinal epithelium. • Blocking this interaction enhances T cell activation and proliferation. RCT:3Q17 HNC ••• CC •/•• •• HNC RCT:3Q17 UCC ••• MM •/•• Keytruda Signal Dendritic Cell CTL io: milestones Cancer IV/SC Celgene/VentiRx Pharmaceuticals (VTX2337) •• OC RCT:3Q17 HCC •• OC •/•• TLR8 Found in endosomes of monocytes, macrophages and mast cells RCT:MY18 BC •• NHL •/•• CD40 CD40L 2016 2017 2018 2019 2020 Company (Drug) Inidication RCT:3Q18 MDS •• DLBCL •/•• Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 SC SCLC PDAC •• AstraZeneca (MEDI-4736/durvalumab) IV TL1A TNFRSF25 Mologen (MGN1703) •• Monospecific mAb PDL1 TLR agonists TLR9 IL-2 Nektar (NKTR-214) ST MY17 RCT:3Q17 NSCLC ••• IT/IV Checkmate (CMP-001) • 1/2 P PDUFA GITR ligand GITR TLRs regulate tissue Expressed in endosomes of monocytes, macrophages and plasmacytoid dendritic cells RCT:3Q17 GASTRIC MCC Altor (ALT-803) + Phase 3 RCT data ••• •• homeostasis and can IL-15 NSCLC NCT02523469 YE18 3 RCT:1Q18 Bristol-Myers Squibb (Opdivo/nivolumab) 1/2 OC ••• HNC • 4-1BB ligand 4-1BB prime APCs to respond 2 Phase 2 RCT data RCT:MY18 RCC ••• MES • to foreign antigens TLR3 IM/IT Oncovir (Hiltonol/poly ICLC) •• MEL IL-7 NCI (CYT107) PC NCT01881867 1Q17 T cell 2 2 Phase 2 data RCT:3Q19 UCC ••• Pfizer/Merck KGaA() IV OX40 ligand OX40 Endosomal TLR expressed in dendritic cells Stimulatory Unknown OncoSec OMSI100 MEL NCT01502293 MY18 Phase 1/2 RCT data Activate Antigen factors growth ST •• IV IL-12 1/2 Novartis (PDR001) Signal 2 ST • Bristol-Myers Squibb (BMS-936559l) IV CD70 CD27 survival IT Immune Design (ID-G100) + IV Merck (Keytruda/pembrolizumab) •/•• NHL Phase 1/2 data NCT02009449 1Q17 1/2 TLR4 SAR IL-10 Armo (AM0010/pegylated IL10) ST 1/2 benefit • 1 Phase 1 data HHLA2 TMIGD2 Expressed predominately on monocytes, mature macrophages and dendritic cells, mast cells IT Immune Design (ID-G100) • MCC ST • Aurigene/Curis (CA-170) PO Presenting Cell GBM NCT02017717 2Q17 Oral PDL1/PDL2/VISTA-targeted and the intestinal epithelium. 3 PoC ICOS ligand ICOS MEL M RCT:1Q20 HNC ••• Class has known overall HCC NCT02576509 3Q17 3 RCT:2Q17 GBM ••• CRC •/•• survival benefit CD86 RCT:1Q18 (APC) Response Local TLR7 and TLR8 TOPICAL 3M Pharmaceuticals/Celldex (resquimod) •/•• NHL Bristol-Myers Squibb (Opdivo/nivolumab) SCLC NCT02538666 2Q18 NSCLC ••• CD28 3 Bristol-Myers Squibb Found in endosomes of monocytes and macrophages, with TLR7 also being expressed on RCT:3Q19 RCC ••• (Yervoy/+Opdivo/nivolumab) IV CD80 administration DIS- plasmacytoid dendritic cells and TLR8 also being expressed in mast cells EC NCT02743494 3Q19 MEL M CONTINUED SCLC Non-epitope-specific activation 3 RCT:MY17 MCC DIS- Signal 1 MHC class II TCR •• CONTINUED NSCLC UCC NCT02632409 3Q20 DIS- IgG1 mAb TOPICAL Medicis/3M Pharmaceuticals (Aldara/imiquimod) M/G BCC 3 OC •• CONTINUED PC CD8+ DIS- Induces ADCC LAG3 TLR7 IB Telormedix (TMX101) •• UCC BC • CONTINUED GASTIC UCC NCT02256436 2Q17 Found in endosomes of monocytes, macrophages and plasmacytoid dendritic cells 3 PDAC • Bristol-Myers Squibb (Yervoy/ipilimumab) IV CD86 CTLA4 Lymph Bristol-Myers Squibb (Yervoy/ipilimumab) IV + IM/TOPICAL Dynavax (SD101) •• BC BC NCT02555657 MY17 RCT:2Q17 MEL M 3 Merck (Keytruda/pembrolizumab) IV CD80 PDL1 IB Exicure (AST-008)  BC PD1 Bristol-Myers Squibb (Yervoy/ipilimumab) IV + TLR9  HL NCT02684292 1Q18 ST • IT Idera Pharmaceuticals (IMO-2125) Roche (Tecentriq/atezolizumab) IV DO NOT DO NOT 3 PDL1 PD1 CD4+ Expressed in endosomes of monocytes, macrophages and plasmacytoid dendritic cells IT Fortress Bio (CMP-001)  Node EC NCT02564263 MY18 RCT:YE17 NSCLC ••• 3 OUT OF DATE. OUT OF DATE.•• BC RCT:MY19 RCT:3Q17 HNC ••• ST •• PDL2 CD80 •/•• MEL Merck (Keytruda/pembrolizumab) MM NCT02576977 3Q18 RCT:3Q17 UCC ••• RCT:4Q17 GEJ •/•• 3 SC Prima Biomed (IMP321) • RCC RCT:YE17 VISTA ? Provide anti-MHCII-LAG3-IgG1 fusion protein HCC •• AstraZeneca (+durvalumab) IV CTLA4-targeted agents HCC NCT02702401 1Q19 3 RCT:3Q19 Promotes APC activation by binding to MHCII OC •/•• IgG2 mAb • CTLA4 competes with CD28 in the lymph node to suppress T-cell activation. • CTLA4 is expressed on Tregs; IgG1 mAb promotes Treg clearance. Promotes APC activation by binding to MHCII DIS- BTNL2 ? NCT02494583 3Q19 CONTINUED MES AstraZeneca (tremelimumab) IV Induces less ADCC than IgG1; potentially reduces release syndrome AE Gastric • Blocking CTLA4 preferentially promotes activation of T cells in the lymph node relative to the tumor • Lower efficacy and safety than targeting PD1/PD- IMP321: MY19 IV Pfizer(PF-04518600) + IV Pfizer/Merck KGaA(Avelumab) • ST 3 ST • Agenus (AGEN2041) IV site. B7-H4 ? Roche (IV RG7888 + IV Tecentriq/atezolizumab) • ST CRC NCT02563002 3Q19  Inhibitory 3 North Coast Biologics IV Roche (RG7888) • ST  Yervoy Signal Antitope B7-H4 ? Educate Dendritic Cells See Immuno-Oncology: Cancer Vaccines IV AstraZeneca (MEDI0562 + durvalumab) • ST RCC NCT02811861 4Q20  1 Tizona Therapeutics Cancer vaccines target immune response against tumor epitopes IV AstraZeneca (MEDI0562) • ST  Butyrophilin famliy ? SCLC NCT02763579 MY19 JHL Biotech/HumOrigin Corp. (JHL-1155) IV GSK (GSK3174998) + IV Merck (Keytruda/pembrolizumab) • ST 3  Aduro Biotech (BION-007) Monospecific mAb IV GSK (GSK3174998) • ST  CD48 CD244 OX40/CD134 agonists CRC NCT02788279 2Q19 Alligator Bioscience (ADC-1015) IV Bristol-Myers Squibb (BMS-986178 + Opdivo/nivolumab) • ST 3  • OX40 is expressed on T cells, NK T cells, neutrophils and and NK cells; T cell expression is transient after • Most potent at stimulating CD4+ helper T cell response. Roche (Tecentriq/atezolizumab) Premier Biomedical IV Bristol-Myers Squibb (BMS-986178) •/•• ST CD155 TIGIT TCR ligation. RCC NCT02420821 3Q20 • Promotes T cell memory response 3  Bristol-Myers Squibb/CytomX Therapeutics •• PC (probody drug conjugates) IV AstraZeneca (MEDI6469) • BC BC NCT02425891 3Q20  Galectin 9 3 BioAtla (CAB-CTLA4) Conditionally-active mAb TIM3 PF-04518600+Avelumab: 1Q18 Alligator Bioscience (ADC-1015)  NCT02352948 2Q17 Phosphatidylserine Agenus/Incyte (INCAGN01949)  NSCLC P  Alligator Biosciences (ADC-1015) Apogenix GmbH  Preclinical programs HNC NCT02551159 3Q17 CTLA4xOX40 BTLA Apogenix GmbH (ox-40 agonist)  3 IV ST DIS- Bispecific antibody AstraZeneca (MEDI6383) • CONTINUED AstraZeneca (durvalumab/MEDI-4736) UCC NCT02516241 3Q17  Hanmi Pharma (CTLA4/TNF-α targeting therapeutics) HVEM CD160 3 CTLA4xTNFα •• CLL Stimulatory Adapted from Freeman,G. et al., Nat Rev Drug Discov (2015) 14, 561-584. PDL1 HCC NCT02519348 3Q17 Siglec Family LIGHT IV Bristol-Myers Squibb () •• NHL 2  Signal IV Pfizer (PF05082566/utomilumab) NCT02725489 MY18 Anaeropharma Sciences (ADC-1015) Bacteria that produce single-chain fragment antibodies in • ST BC + IV Pfizer/Merck KGaA(Avelumab) 2 hypoxic sites IV Pfizer (PF05082566/utomilumab) • ST NSCLC NCT02395172 3Q17 + IV Merck (Keytruda/pembrolizumab) 3 ST 4-1BB/CD137 agonist mAbs • Gastric NCT02625623 3Q17 3 overall survival 4-1BB/CD137 agonist mAbs IV Pfizer (PF05082566/utomilumab) • NHL • 4-1BB is expressed on T cells and NK cells. • Promotes activation and proliferation of T cells Bristol-Myers Squibb (IV Urelumab + IV Opdivo/nivolumab) • ST OC NCT02580058 1Q18 3 Vemurafenib (N=336) Apogenix GmbH (4-1bb agonist)  Activate T cell response Pfizer/Merck KGaA (Avelumab) 100 Utomilumab +Avelumab: YE17  RCC NCT02684006 MY18 Dacarbazine (N=336) Bioinvent International 3 Inhibit T-cell immune Multimeric Biotherapeutics  Inhibition of T cell immune evasion 90 Provide T-cell costimulatory UCC NCT02603432 3Q19 3 Bristol-Myers Squibb (IV BMS-986156 + IV Opdivo/nivolumab) • / • • SHT evasion pathways factors Novartis (IV GWN323 + IV PDR001) • / • • SHT MCC NCT02155647 3Q17 2 80 • Provide the ‘second signal’ after TCR engagement to induce IV Incyte/Agenus (INCAGN1876) •/•• ST Immune signals are weakened as a result of immune Bristol-Myers Squibb (Yervoy/ipilimumab) MCC NCT02196961 MY17 proliferation of existing antigen-specific T cells Merck (IV MK-1248+ IV Keytruda/pembrolizumab) • ST 2 cell exhaustion or immunosuppressive elements of the CTLA4 70 • Can be optimized to clear Tregs via ADCC IV Leap Therapeutics (TRX-518) • MEL tumor microenvironment; can be optimized to clear AstraZeneca (tremelimumab) OC NCT02485990 3Q19 1/2 GITR/TNFRSF18 agonist mAbs IV Merck (MK-4166) • ST regulatory T cells via ADCC IV AstraZeneca (MEDI1873) • ST NCT02017717 2Q17 60 GBM 3 GITR is expressed on T cells, B cells, NK cells, and dendritic cells. IV Amgen (AMG 228) • ST • Enhances effector T cell proliferation and blocks Treg cell-mediated immunosuppression • GITR is constitutively expressed on Tregs Fortress Bio/TG Therapeutics (anti-GITR)  NSCLC NCT02477826 1Q18 3 50 Regeneron/Sanofi(anti-GITR)  Bristol-Myers Squibb BMS986156+Opdivo: MY18  SCLC NCT02538666 2Q18 Merck (mDTA-1) PD1 + (Opdivo/nivolumab + Yervoy/ipilimumab) 3 Bristol-Myers Squibb (BMS-986016 IV + IV Five Prime Therapeutics (FPA154)  CTLA4 40 ST • RCC NCT02231749 3Q19 Opdivo/nivolumab IV) IV OncoMed Pharmaceuticals (GITRL-Fc)  3 ST • Bristol-Myers Squibb (BMS-986016) IV ST HNC NCT02741570 1Q20 Overall Survival (%) IV Celldex () + IV Bristol-Myers Squibb (Opdivo/nivolumab) • 30 ST • Novartis (IMP701 + PDR001) IV 3 Anti-LAG3 mAbs IV IV RCC ST • IV efficacy Celldex (varlilumab) + Roche (Tecentriq/atezolizumab) • / • • Merck (Keytruda/pembrolizumab) + GSK (GSK2831781) MEL NCT02506153 YE17 • LAG3 functions as a negative regulator for T cell responses to MHC class II-presented antigens. • Along with PD1, LAG3 is expressed on exhausted T cells CD27 agonist mAbs IV Celldex (varlilumab) •/•• SHT Bristol-Myers Squibb (Yervoy/ipilimumab) 20  Tesaro (LAG-3 antibody) 3  • Blocks Treg cell-mediated immunosuppression 100 CD27 is expressed on most effector T cells, some NK cells and some B cells Apogenix GmbH (CD27 agonist)  Agenus/Incyte (LAG-3 checkpoint modulator) HNC NCT02551159 3Q17  • Drives germinal center formation via CD4+ T cells • The CD27 ligand CD70 is present on activated T and B cells, dendritic cells and macrophages. Aduro BioTech (BION-1402)  3 10 MacroGenics (MGD013) BMS-986016+Opdivo: 2Q18 Pfizer/Merck KGaA (avelumab) UCC NCT02516241 3Q17 3 Hazard Ratio: 0.37 (95% CI, 0.26-00.55) P<0.001 varlilumab+Tecentriq: YE17 AstraZeneca IV 90 AstraZeneca (durvalumab/MEDI-4736) PDL1 + NSCLC NCT02352948 YE17 0 ST MacroGenics (Enoblituzumab/MGA271) + (durvalumab/MEDI-4736+ tremelimumab) • IV PDL1: CTLA4 3 Merck (Keytruda/pembrolizumab) Roche (Tecentriq/atezolizumab) Months: ST • IV RELY UPON. RELY UPON.HCC NCT02519348 1Q18 0 1 2 3 4 5 6 7 8 9 10 11 12 MacroGenics (Enoblituzumab/MGA271) Anti-B7-H3 mAbs TNFRSF25/DR3 fusion protein Pelican Therapeutics (PTX-25A)  2 BRAIN • Y-mAbs Therapeutics (8H9 Mab) IV Bristol-Myers Squibb (BMS-936559) TL1A-Ig fusion B7-H3 shows some homology to PDL1 and is expressed on inhibitory cells. • Present on T cells, especially memory T cells. • The TNFRSF25 ligand TL1A is expressed on APCs. NCT02340975 4Q17 ST • Daiichi Sankyo (DS-5573a) IV 80 GEJ 1/2 Bristol-Myers Squibb Enoblituzumab+Keytruda: 3Q18 ST NCT01968109 2Q18 Dacarbazine 336 283 192 137 98 64 39 20 9 1 1 0 0 Merck (Keytruda/pembrolizumab) LAG3 (BMS-986016 +Opdivo/nivolumab) 1 PD1: MacroGenics (Enoblituzumab/MGA271) + Bristol-Myers Squibb (Opdivo/nivolumab) B7-H3 ST NCT02475213 3Q18 Vemurafenib 336 320 266 210 162 111 80 35 14 6 1 0 0 ST • Novartis (MBG453 +PDR001) IV 70 Celgene/Jounce Therapeutics (JTX-2011) •/•• Merck (Keytruda/pembrolizumab) 1  GSK (GSK3359609)  Tesaro (TSR-022) Novartis (MBG453 +PDR001) ST NCT02608268 MY18  TIM3 1 Chapman, P.B., Hauschild, A., Robert, C., Haanen, J.B., Ascierto, P., Larkin, J. et al, Improved survival with vemurafenib in melanoma with BRAF V600E mutation.  Agenus (TIM3 antibody) Anti-TIM3 mAbs INSERM  N Engl J Med. 2011;364:2507–2516.  Cellerent (TIM3 antibody) • TIM3 is expressed on T cells, NK T cells, and APCs, and is co-expressed with PD1 on exhausted T • TIM3 may block enhanced signaling via GAL9. ICOS agonist mAbs MSKCC VISTA ImmuNext/Janssen (JNJ-61610588) ST NCT02671955 2Q18  1  Merus (MCLA-134) cells. 60 • Expressed on activated T cell • The ICOS ligand is expressed on B cells, APCs and some tumor cells. Bristol-Myers Squibb NCT02346955 2Q19  Enumeral (TIM3 program) CEACAM1 Merck (CM-24) ST 1 MBG453+PDR001:MY18 Galectin (GR-MD-02) + MEL NCT02575404 1Q18 Galectin-3 Merck (Keytruda/pembrolizumab) 1 50 Corvus  overall survival OX40 Pfizer (PF-04518600) + Pfizer/Merck KGaA (Avelumab) ST NCT02554812 1Q18  Roche Anti-TIGIT mAbs Selectively inhibit ITK Confluence Life Sciences  1 • TIGIT is expressed on exhausted NK and T cells. • Inhibiting TIGIT enhances activation of NK cells and T cells Pfizer (utomilumab/PF05082566;IV) + 4-1bb ST NCT02179918 1Q17 Inhibit ITK  Pfizer/Merck KGaA (Avelumab) 1 N N20 Induce CTL response by Principia Biopharma 00 • Promotes Th1 differentiation; enhances activation and tumor uptake by APCs  T cell Bristol-Myers Squibb 40 Takeda factors ST NCT02598960 MY18 N20 GITR (BMS-986156 + Opdivo/nivolumab) 1 • May inhibit NK cells  Class has unknown survival promoting differentiation of Bristol-Myers Squibb costimulatory 90 Unknown selectivity for ITK  NCT02543645 YE17 benefit Novartis CD27 Celldex (varlilumab) + Roche (Tecentriq/atezolizumab) ST 1/2 ST • IV Th1-dominant helper T cells Higher potential for off-target AEs  ImmuNext/Janssen (JNJ-61610588) GSK Innate Pharma/Bristol-Myers Squibb 0 Anti-VISTA mAb Disinhibit NK cells ST NCT01592370 YE17 30  (lirilumab + Opdivo/nivolumab) • VISTA is expressed on MDSC and Tregs. • Inhibiting VISTA increases proliferation and activation of T cells. Sanofi 2 Overall Response Rate (%)

0 Target Activate NK cells Nantkwest (aNK/NK-92) AML NCT00900809 YE16 NK cells 1 JNJ-61610588:2Q18 Broadly acting NCT01265849 YE17 60 20 cytokines CEL-SCI (Multikine) HNC 3 Arcus Biosciences  Alpine Immune Sciences  TGFβ inhibitors Eli Lily (galunisertib/LY2157299) ST NCT02304419 MY18 0 Merck/cCAM Biotherapeutics 2 ST •/•• Compass Therapeutics  (CM-24 + Keytruda/pembrolizumab) IV Incyte (epacadostat/INCB24360) + iDO inhibitors MEL NCT02752074 MY18 Harpoon Therapeutics  Merck (Keytruda/pembrolizumab) 40 ST •/•• Merck (CM-24) IV Anti-CEACAM1 mAbs 10 3  ImmuneXcite  Agenus • Expression of CEACAM1 on tumors cells can inhibit CTL and NK cells. • CEACAM1 is associated with poor prognosis. PDAC NCT02362048 MY17  2 30 Antibody/antibody-like discovery programs (undisclosed Kymab Target MDSCs Acerta (acalabrutinib/ACP196) +  Merck (Keytruda/pembrolizumab) OncoResponse NCT02351739 MY17 CM-24:2Q19 targets) UCC microenvironment 2 20 Trellis Bioscience  Reverse suppressive Reverse suppressive § ¥ 9 4 Zymeworks  Target T-regs Corvus (CPI-444) + Roche (Tecentriq/atezolizumab) ST NCT02655822 3Q17 13 17 14 41 15 17 15 17 42 23 52 54 78 92 64 31 59 25 59 23 26 75 25 55 Number of 99 11 1/2 101 192 168 240 667 210 278 821  0 IV 138 Applied Immune Technologies MEL Galectin Therapeutics (GR-MD-02) + Patients • IV Unpartnered 02 CI 2 to 000 Merck (Keytruda/pembrolizumab) Anti-Galectin-3 mAbs SIRPα/CD47 Trillium Therapeutics (TTI-621) HM NCT02663518 YE17 MEL • IV T cell 1 0 Galectin Therapeutics (GR-MD-02) • Soluble Galectin-3 is over-produced by tumor cells. • Inhibiting Galectin-3 signaling enhances clonal expansion of T cells and prevents anergy. Indication GBM PC OC PDAC BC BCL RCC HNC HCC MES MCC UCC PDAC MSI CRC CRC MSI SCLC ESO GASTRIC NSCLC MEL Lymphoma NextCure  60 Target M2 Roche (emactuzumab/RG-7155 + 0 3 6 9 2  Disinhibit ST NCT02760797 3Q18 GR-MD-02+Keytruda: 1Q18 Undisclosed platform Torque Therapeutics macrophages Tecentriq/Atezolizumab) 1 PC •• Preclinical IO platforms  (95% CI) DLBCL •• Ablynx/Merck Pattern Low Medium/Unknown High Compugen/Bayer  Recognition Novartis/Aduro (ADU-S100) ST NCT02675439 MY17 1 N 21 1 1 1 4 020 not reached RCC •• Receptors F-star/AbbVie  FL •• APCs Target Antibody/antibody-like discovery programs (undisclosed  2 1 123 2 22 3 9620 0 (9.3-12.1) GLI IV Morphosys/Merck KGaA CD40 Roche (RG7876+Tecentriq/atezolizumab) ST NCT02304393 YE17 •/•• Medivation/CureTech (/CT-011) Partnered Activate 1 Unknown target targets) Sutro Biopharma/Celgene  Robert C Lon Brady B utriaux C Maio M Mortier L et al Nivolumab in previously untreated melanoma without BRAF mutation. 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