Vice President, Cancer Immunology @CytomX Therapeutics, Inc. CD3-EGFR Probody™ T Cell-engaging Bispecific Induces Tumor Regressions and Increases Safety Window in Preclinical Studies Bryan A. Irving Ph.D. Vice President, Cancer Immunology @CytomX Therapeutics, Inc.

Presenter Disclosure Information Bryan A. Irving Ph.D. The following relationships exist related to this presentation: CytomX Therapeutics, Inc. (Employee)

T-Cell Engaging Bispecifics T-cell Engaging Bispecific Therapeutics: Highly Potent, but Associated with Safety Liabilities T-Cell Engaging Bispecifics T-cell Engaging Bispecific Antibodies (Ab-TCBs) Bring cytotoxic T cells & cancer cells together Highly potent but toxic modality – unforgiving for target expression on normal tissue EGFR/CD3 BiTE in cynomolgus monkeys.1 Kidney and liver toxicity, cytokine storm, inflammatory cell infiltrates in EGFR-expressing organs EpCAM/CD3 Catumaxomab: drug-related fatal hepatic failure at 10ug dose (trial terminated).2 Challenging to use for solid tumors Target Cell T Cell Nature Biotechnology 23, 1065 - 1072 (2005) 1Lutterbuese et al., (2010) PNAS 107: 12605 2Mau-Sorensen, M et al. Cancer Chemother Pharmacol (2015) 75: 1065-73

Probody™ Therapeutics are Designed to be Activated in the Tumor Microenvironment ANTI-CANCER ANTIBODY PROTEASE-CLEAVABLE LINKER MASKING PEPTIDE PROTEASES Well-established that upregulated protease activity is a hallmark of most if not all cancers, while proteases are tightly controlled in normal tissues. The Probody platform aims to take advantage of this distinction by engineering a protease-activatable substrate into a recombinant antibody CytomX Probody linkers are designed to be cleaved by multiple proteases for utility across tumor types PROBODY is a trademark of CytomX Therapeutics, Inc. All other brands and trademarks referenced herein are the property of their respective owners.

EGFR-dependent Cytotoxicity EGFR/CD3 Probody TCB Attenuates Cytotoxicity >1000x in vitro that is Fully Recovered by Protease Treatment Probody Bispecific (Pb-TCB) Protease-cleaved, Recovered potency >1000x EGFR-dependent Cytotoxicity Fc effector mutant(s) a-CD3 scFvs a-EGFR Protease cleavable linker mask

EGFR/CD3 Probody TCB Induces Regressions of Established HT-29 Tumors in T-Cell Engrafted NSG mice Ab-TCB Pb-TCB Dose-dependent activity Ab-TCB & Pb-TCBs demonstrate comparable anti-tumor activity @1mpk.

Concentration TCB in Plasma Probody TCBs Protect from Cytokine Release and Organ Toxicity While Extending PK in Cynomolgus Monkeys IL-6 ~33x Concentration TCB in Plasma Pb-TCB >300 Fold Higher Exposure Than Toxic Ab-TCB >300X Dose (mg/kg) ~33x AST Dose (mg/kg)

EGFR Probody TCBs Expand Therapeutic Window in Preclinical Studies Efficacy: Potent tumor activity despite strong masking Attenuates target binding and T cell cytotoxicity >1000-fold in vitro under protease-deficient conditions Is highly effective in vivo, eliminating established tumors Safety: Reduced cytokine and organ toxicities despite high exposure Probody TCB MTDs are >30 times that of the corresponding antibody TCB Tolerated Probody TCB serum concentrations are >300 times than for toxic antibody TCB dose Probody technology has the potential to protect normal tissues and expand utility for bispecifics, especially for solid tumors

Acknowledgements Sherry L. La Porte Daniel R. Hostetter Laurie Wong O. Jennifer Razo Linnea Diep Clayton W. White Jennifer H. Richardson W. Michael Kavanaugh CytomX Therapeutics, Inc.