CSF1R Antibody LY , IMC-CS4. Drug Discovery Platform: Immuno-Oncology. Derived from Pixley FJ and Stanley ER. 1

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1 CSF1R Antibody LY , IMC-CS4 Derived from Pixley FJ and Stanley ER. 1 Drug Discovery Platform: Immuno-Oncology

2 A Phase 1 Study to Identify the Immunomodulatory Activity of LY (IMC-CS4) in Patients With Advanced, Refractory Breast or Prostate Cancer* Breast cancer Key Inclusion Criteria Key Exclusion Criteria Advanced, refractory breast or prostate cancer that is evaluable by radiologic testing. Participants must have experienced tumor progression on, or treatment intolerance to, at least one prior therapy Symptomatic central nervous system malignancy or metastasis Adequate organ function, including bilirubin 1.5 the upper limit of normal (ULN), alanine aminotransferase and aspartate transaminase 3.0 ULN (5 ULN acceptable for known liver metastases), and serum creatinine 2.0 ULN Eastern Cooperative Oncology Group (ECOG) performance status of 2 Willing to undergo pre- and posttreatment tumor biopsies Prostate cancer Active fungal, bacterial, and/or known viral infection, including HIV or hepatitis B or C History of and/or current symptomatic coronary artery disease, including confirmed left ventricular ejection fraction 50% or uncontrolled hypertension (>170/100 mm Hg) Please visit for more information on this clinical trial [NCT ]. * This clinical trial is being conducted in the United States. Primary endpoint: Immunomodulatory activity of LY treatment with similar cumulative doses across two groups Participants continue study treatment until development of progressive disease. 2 3

3 A Phase 1a/1b Trial Investigating the CSF1R Inhibitor LY in Combination With Durvalumab (MEDI4736) or Tremelimumab in Patients With Advanced Solid Tumors* Key Inclusion Criteria Key Exclusion Criteria Cancer that is not amenable to curative therapy Currently receiving or has taken an immunosuppressive medication within 28 days prior to first dose of study drug, excluding intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid Part B: Must have a type of malignancy that is being studied Must be willing to undergo pretreatment and on-treatment core needle or excisional tumor biopsies Part A: Measurable and/or nonmeasurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 Part B: Measurable disease as defined by RECIST version 1.1 Adequate hematologic and biochemical parameters Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Symptomatic central nervous system malignancy or metastasis Part A : Dose escalation durvalumab Part A : Dose escalation tremelimumab Part B : Dose expansion durvalumab Part B : Dose expansion tremelimumab Prior grade 3 immune-related adverse event (irae) while receiving any previous immunotherapy agent, have any unresolved irae grade >1, or any irae that led to the permanent discontinuation of prior immunotherapy Experienced a grade 3 adverse event (AE), or a neurologic or ocular AE of any grade while receiving prior immunotherapy Please visit for more information on this clinical trial [NCT ]. * This clinical trial is being conducted globally in partnership with AstraZeneca. Primary endpoint: Safety, tolerability, and recommended phase 2 dose of LY in combination with durvalumab or tremelimumab Participants continue study treatment until disease progression or discontinuation criteria are met. LY , durvalumab, and tremelimumab are administered intravenously. 4 5

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5 Target Molecule Colony-stimulating factor 1 receptor (CSF1R), also known as macrophage colony-stimulating factor receptor (M-CSFR), is a cellsurface receptor for its ligands, colony-stimulating factor 1 (CSF1) and IL-34.1,2 CSF1R plays an important role as regulator of the development, morphology, survival, and functions of tissue macrophages as well as tumor-associated macrophages (TAMs). CSF1 is involved in the recruitment and survival of macrophages in tumors. Increased CSF1 expression is implicated in tumor progression and metastasis, and is associated with poor prognosis in some cancers.3 LY (IMC-CS4) is a human IgG1 monoclonal antibody designed to target the CSF1R, preventing ligands CSF1 and IL-342 from binding to the receptor and inhibiting TAMs from receiving CSF1 signals, decreasing their survival and relieving the effect of TAMs in the tumor.4 Clinical Development LY (IMC-CS4) is being investigated in phase I clinical trials, including a collaboration clinical trial with another immuno-oncology agent. Study Schemas Not Available [NCT ] Early Development A Study of IMC-CS4 in Subjects With Advanced Solid Tumors References: 1. Pixley FJ, Stanley ER. Trends Cell Biol. 2004;14(11): Lin H, et al. Science. 2008;320(5877): Aharinejad S, et al. Cancer Res. 2004;64(15): Data on file. Eli Lilly and Company: ONC A. ON /2016 PRINTED IN USA Lilly USA, LLC All rights reserved.