CCO Independent Conference Coverage* of the 2016 ASCO Annual Meeting, June 3-7, 2016 Phase II MONARCH 1: CDK4/6 Inhibitor Abemaciclib in HR+/HER2- MBC After Chemotherapy *CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs. This activity is supported by educational grants from Amgen, Ariad, Bayer Healthcare Pharmaceuticals, Celgene Corporation, Genentech, Incyte, Merck, and Taiho Pharmaceuticals.

MONARCH 1: Abemaciclib in Refractory HR+/HER2- MBC  CDK4 and CDK6 important targets in breast cancer [1,2]  Abemaciclib: selective inhibitor of CDK4 and CDK6 [3] –Phase I: abemaciclib active as single agent in pts with heavily pretreated HR+ MBC [4]  For pts with HR+/HER2- MBC who have been previously treated with taxanes and require additional chemotherapy, median PFS is 3-4 mos with current cytotoxic chemotherapy options [5]  MONARCH 1 evaluated safety and efficacy of abemaciclib in this pt population [6] 1. Altucci L, et al. Oncogene. 1996;12: Gelbert LM, et al. Invest New Drug. 2014;32: Lallena MJ, et al. Cancer Research. AACR Abstract Patnaik A, et al. Cancer Discov. 2016;[Epub ahead of print]. 5. NCCN clinical practice guidelines in oncology: breast cancer. v Dickler MN, et al. ASCO Abstract 510. Slide credit: clinicaloptions.comclinicaloptions.com

Phase II MONARCH 1: Abemaciclib in Previously Treated HR+/HER2- MBC  Treatment: abemaciclib 200 mg PO every 12 hrs until unacceptable toxicity or PD  Inclusion criteria (N = 132) –Progression on or after endocrine therapy –≥ 2 previous chemotherapy regimens (≥ 1 for metastatic disease and ≥ 1 with taxane; no previous treatment with CDK4/6 inhibitors) –ECOG PS 0 or 1 –Measurable disease (RECIST v1.1) –No current or previous CNS metastasis  Primary endpoint: ORR by investigator assessment (RECIST v1.1)  Secondary endpoints: DoR, PFS, OS, CBR, safety Slide credit: clinicaloptions.comclinicaloptions.com Dickler MN, et al. ASCO Abstract 510.

Abemaciclib in HR+/HER2- MBC (MONARCH 1): Baseline Characteristics Slide credit: clinicaloptions.comclinicaloptions.com Dickler MN, et al. ASCO Abstract 510. CharacteristicPts (N = 132) Median age, yrs (range) 58 (36-89) Age 65 yrs of age or older, % 31.8 ECOG PS 0/1, %55.3/44.7 Metastatic sites, %  Visceral (liver/lung)  Bone 90.2 (70.5/23.5) 62.1 No. of metastatic sites, %  < 3  ≥ Median previous therapies, n (range)  Any setting  Metastatic setting 5 (2-11) 3 (1-8) ≥ 2 previous regimens for metastatic disease, %  Endocrine therapy  Chemotherapy Notable previous regimens for metastatic disease, %  Fulvestrant  Taxane  Capecitabine

Abemaciclib in HR+/HER2- MBC (MONARCH 1): ORR Slide credit: clinicaloptions.comclinicaloptions.com Dickler MN, et al. ASCO Abstract Change From Baseline (%) Disease control rate (CR + PR + SD) = 67.4% * Assessments based on independent review were comparable. PD (n = 34) SD (n = 63) PR (n = 26) Not assessed (n = 9) Investigator Assessed Response * Abemaciclib 200 mg (N = 132) Confirmed ORR, % (95% CI)19.7 ( ) CR, %0 PR, %19.7 SD ≥ 6 mos22.7 CBR (CBR = ORR + SD ≥ 6 mos)42.4

Abemaciclib in HR+/HER2- MBC (MONARCH 1): Secondary Endpoints  Median time to response: 3.7 mos  Median DoR (from first documented response): 8.6 mos –6-mo DoR rate: 70.4% –12-mo DoR rate: 28.2%  Median PFS: 6.0 mos (95% CI: )  Median OS: 17.7 mos (95% CI: 16.0-NR)  CBR: 42.4% Slide credit: clinicaloptions.comclinicaloptions.com Dickler MN, et al. ASCO Abstract 510.

Abemaciclib in HR+/HER2- MBC (MONARCH 1): Safety  Most common treatment-related AEs (> 20%): diarrhea, fatigue, nausea, decreased appetite, abdominal pain, vomiting, headache  Most common lab abnormalities (> 40%): creatinine increase, WBC decrease, neutrophil count decrease, anemia, platelet count decrease  49.2% of pts had dose reductions, most commonly from diarrhea (20.5%) or neutropenia (10.6%) Slide credit: clinicaloptions.comclinicaloptions.com Dickler MN, et al. ASCO Abstract 510. AE Category, n (%)Pts (N = 132) Serious AE32 (24.2) AEs leading to study drug discontinuation10 (7.6) AEs with outcome of death  During therapy  Within 30 days of study discontinuation 3 (2.3) 2 (1.5) 1 (0.8)

Abemaciclib in HR+/HER2- MBC (MONARCH 1): Conclusions  Abemaciclib monotherapy active in heavily pretreated pts with HR+/HER2- MBC  Safety and toxicity profile consistent with that of previous studies, with few discontinuations  Phase III studies of abemaciclib + endocrine therapy (MONARCH 2, MONARCH 3) ongoing Slide credit: clinicaloptions.comclinicaloptions.com Dickler MN, et al. ASCO Abstract 510.

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