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Indication 1 Uterine Uterine (carcinosarcoma) Lung Lung (adenocarcinoma) Reid Reid (cutaneous)Melanoma abe2cb4efdbde42fab6c00d84cb1a578_UP000063_1. identifiedby AlaScanisshown. isbasedonStructure crystal murinestructure epitopeHDXof INCAGN02390 hTIMon predicted TIM (AlaScan).BasedHDXon characterization, INCAGN02390 occludes the of CC’/FGhuman loops TIM Modelingthebinding of of humanINCAGN02390 onsite TIM from peripheralfrom blood of healthypatientscancer or patients. Representative flow cytometry histogramsdemonstratingTIM wholegenome RNA Median Priyadarshini Cervical Cervical (squamous) RCC RCC (chromophobe) Cholangiocarcinoma Lymphoma (DLBC) Lymphoma Pancreatic Pancreatic (ductal) Bladder Lung Lung (squamous) (PS, HMGB1, (PS,HMGB1, Ligand pocket Breast Breast (invasive) Uterine Uterine (corpus) Leukemia (AML)Leukemia RCC RCC (clear cell) Head Head and Neck RCC RCC (papillary) shown: Adrenocortical Brain Brain (glioma) M Brain Brain (PCPG) Brain Brain (GBM) Esophageal Φ Predicted Predicted interaction onbased HDX and Thymoma , Testicular - INCAGN02390ObstructstheFG/CC’Binding TIMCleftof Sarcoma geneexpression of TIM Urothelial Stomach macrophages; NK, regulatory macrophages; T cells; natural killer Treg, Prostate Rectum Ovarian Huber, Thyroid Colon HCC CEACAM1 TIM Renalcell( carcinoma - 3 interactions.ligand FG loop 0 Front TIM ) - - seq 2 3 CC’ CC’ loop - 3 ( Robert of 11,000 of patientbiopsiestumor 31 across tumor Is Iyer, Human Human TIM HAVCR2 Median Median (Normalized Lexington 10 Expresseda RangeinHumanof - 3 types invarioustumor 1 AlaScan RCC; Ekaterina Stein, ) TCGA TCGA ) Data , MA; MA; , and - - 3 3 extracellular3 domain( Expression stage I), stage I), C cells. ounts) 2 20 Back Incyte 1 InfiltratingCellsImmune Marc Marc van N=8 separate separate N=8indications(and characterizedindividual4 samples). RCC Corporation, Epitope Breous profiled 30 - - 3 as by determineddeuteriumhydrogenexchange (HDX)and Alanine scanni 3 expressionvariousimmuneon within populationsthe microenvitumor identifiedPepscanby is green imntn DE Wilmington, by TheCancerGenome expressionwas determinedAtlas(TCGA). Gene using Dijk, - B B Nystrom, and types. types. magenta 1 Flow Flow cytometry: Example Example TIM PDB Jennifer Buell, Healthy Donor Healthy and and Tumor Matchedandtumor patient cancer blood ( HDX HDX 2OYP modeled2OYP to humanSwissModel sequence:entry ); highestdifference inHDX ); ( 1 overlaid Peripheral Blood Peripheral / AlaScan Christina in - - 3 Expression on red Infiltrating . Malignancies - 3, 3, potentiallyinterferingwithmul 1 Riordan, Nicholas Nicholas Cancer Patient Cancer magenta Immune Immune Cells Overlay Pepscan ); sidechain of sidechain of Phe40 ); Peripheral Tumor 1 RCC stage I stageRCC David David A. S. S. Wilson (red) Cells - - Infiltrating 3 omn and ronment tiple ) ng i.d. Savitsky, 1 APC, antigen presenting cell; cell; APC,presenting antigen major MHC, TCR, histocompatibility T complex; B. A. A A B A INCAGN02390 MFI, mean fluorescence intensity. MFI, mean fluorescence binding of binding of humancynomolgus or TIM cellsby was detected flow cynomolgus CD14+myeloidfrom cynomolgus and cellshumanperipheral monkeyblood mononuclear cells ( Dose INCAGN02390 Cooperates WithINCAGN02390 Cooperates 1 INCAGN02390Demonstrates Mark Mark donor PBMCs were stimulated with 100 IFN of human An (Promega) was used to assess internalization.For microscopy, each antibody was used at 10 Kinetic of analysisINCAGN02390 CellTiter unconjugated INCAGN02390 or isotypecontrol days. for 3 Internalization was indirectlyassessedby viability of Jurkat Dose - dependent Dose illustration functionalof effects theelicited TIM by γ Viability (± SEM), % - 100 A productionSEAfrom dependentTIM 20 40 60 80 MFI MFI 0 0.0001 1000 2000 3000 4000 - monkeyTIM 100 150 200 250 Findeis, Glo 50 PBMCs. - - 0 0 0.0001 0.001 eitd TIM mediated Dependent TIM ® binding of (PromegaCorporation, Madison, WI). 0.001 0.001 INCAGN02390ElicitsRapidInternalizationTIMof INCAGN02390 controlIsotype 0.01 T - - Cell Cell - 3 (Fc) binding to irradiatedmouse WR19L (PS, cellsinduced by 0.01 3 internalization by INCAGN02390.Jurkat Antibody, Antibody, cytometry. Thespeciescross 0.01 1 phycoerythrin 0.1 - Antibody, Dennis Dennis 3 internalization characterizedby - tmltdhmn PBMCshumanfollowingstimulated blockadewithINCAGN02390 and/or 0.1 Binding 1 0.1 μ μ - g/mL g/mL - 1 3 Internalization - 3 Fc to target 3 to Fctarget nue TIM induced μ Blockadeof g/mL 10 - INCAGN02390 INCAGN02390 + ADC Isotype + ADC control INCAGN02390 Isotype control conjugated 10 ng/mL 1 Underwood, B - cell receptor. cell 100 100 IFNg (Fold-Change) SEA + antibody for 8 days. 10 B 0 2 4 6 8 - 0.001 cells 3 internalizationhigh by

INCAGN02390isotype to or control MFI MFI 1200 1600 2000 1200 - 400 800 400 800 . reactivityallowed theof of PSuse irradiated - 0.00001 100 3 andPD 0.01 0 0 0.0001 Myeloid Myeloid 0.0001 0.001 Antibody, (A) (A) INCAGN02390 controlIsotype 0.1 Donor 1 PS Dose 1 - antibodydrugconjugate(ADC) 0.001 0.01 1 blockade followingblockade1staphylococcal enterotoxin A(SEA peptide, - TIM Joseph Anti Antibody, Antibody, B 1 0.01 - μ 0.1 - Cell Cell Binding g/mL TIM 3 Co + - IFN otn microscopy. contentHaloTag cells were were cells auristatinexposedto monomethyl E 0.1 - 10 1 Minutes – High Dependent μ μ γ PD INCAGN02390 Isotype Control g/mL g/mL - production was assessed by AlphaLISA (Perkin 10 1 3 100 Connolly, - 100 Content Microscopy 10 - Interactions - 15 15 1 1000 (A) (A) 100 30 Gy Gy of 30irradiation). IFNg (Fold-Change) Inhibitory 0 2 4 6 8 to EnhanceT 0.001 CD3/CD28 PBMCs).  g/mL. - 0.01 and m 1 60 60 ouse WR19Lousereduce to potential off Binding to TIMBindingto Benjamin Benjamin Morin, - (B) (B) Antibody, anti tmltd CD3+ cellsstimulatedT or C ® ( 0.1 Donor 2 C) technology microscopy – PD Inhibition of

Binding of TIM PS Binding, % PS Binding, % 100 100 - 1 1 20 40 60 80 20 40 60 80 μ 0 0 g/mL 120 120 Post (pembrolizumab, 5 TIM 10 (engineered Jurkat - basedinternalization analysis. - - recombinant andhuman - Cell FunctionCell - 3:PS 3:PS Benchmark antibodyBenchmark INCAGN02390 controlIsotype antibody Addition TIM - 100 conjugated or Antibody, Antibody, - - 3 Fc to irradiated3 to Fcmurine 1 - 1 - 3 3 180 180 Elmer + Blockade cellsusing (B) (B) INCAGN02390 + anti INCAGN02390 + Isotype + anti control INCAGN02390 Isotype control sAg) stimulationsAg) , , Llantrisant, μ 1 ReceptorTIM μ - μ g/mL g/mL M unstimulated g/mL). g/mL). 3 and3 - TIM - ichele ichele Sanicola target target 240 10 10 - 3 Healthy + cells UK ). – – PD PD - - 1 1 2012;13:832 1. References Editorial,graphics, andprinting support wasprovided by Evidence Scientific Solutions Inc. (Philadelphia, PA), funded Acknowledgments by In employment Waight,Iyer,Breous Disclosures • • • • • way ANOVA or Student Tumorgrowth curves miceindividualfor shownin are assessedwithwithoutand bi detected flow cytometry.by binding(human Fc) IgG to irradiatedmouse WR19Lcells inducedof 30 (PS, irradiation). by Gy Binding of TIM (mIgG2a mIgG2a and Characterization of Fc C B A ADCC, antibody ADCC, Huang YH,et significant tumor control when combinedwithwhentumorcontrolsignificant the In INCAGN02390with combines INCAGN02390 inducesrapidinternalization,disrupting TIM potentiallyreceptor multiple INCAGN02390 INCAGN02390fully isa human - Murine Murine Antibody Blocks TIM Nadel, andstock ownership – 42. MC Generating Generating an - IncreasedEfficacyWith dependent cell Comparable Comparable INCAGN02390 Anti Ligand al. 4. -

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