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0916-PER-01 Product Information 420 PERJETA Vial 420mg Pertuzumab 000942 - PERJETA PERJETA PERJETA PERJETA - 1 1.1 PERJETA Herceptin (trastuzumab) docetaxel HER2 HER2 1.2 PERJETA Herceptin (trastuzumab) docetaxel HER2 ( 2 cm ) [ ( 14.2 ) ( 2.1 )] PERJETA doxorubicin 6 PERJETA 2 2.1 PERJETA 840 mg 60 3 420 mg 30 60 Herceptin PERJETA Herceptin 8 mg/kg 90 3 6 mg/kg 30 90 PERJETA Herceptin docetaxel PERJETA Herceptin Docetaxel PERJETA Herceptin PERJETA 1

Herceptin docetaxel 30 60 [ (5.3)] (MBC) docetaxel PERJETA docetaxel 75 mg/m 2 3 100 mg/m 2 3 PERJETA 3 6 [ ( 14.2 )] 2 (NEOSPHERE) PERJETA Herceptin docetaxel 4 fluorouracil epirubicin cyclophosphamide (FEC) 3 3 (TRYPHAENA) FEC 3 PERJETA docetaxel Herceptin 3 3 (TRYPHAENA) PERJETA docetaxel carboplatin Herceptin (TCH) 6 ( docetaxel 75 mg/m 2 ) Herceptin 1 PERJETA 6 anthracycline PERJETA PERJETA doxorubicin 2.2 6 PERJETA 420 mg ( ) 6 PERJETA 840 mg 60 3 30 60 420 mg Herceptin PERJETA PERJETA Docetaxel docetaxel (LVEF) PERJETA Herceptin 3 45% LVEF 45% - 49% 10% [ (5.2)] LVEF 49% 45% - 49% 10% PERJETA 2

3 PERJETA Herceptin [ (5.2)] PERJETA [ (5.3)] / [ (5.4)] 2.3 PERJETA PERJETA 250 ml 0.9% (PVC) (non-pvc polyolefin) 2 C - 8 C 24 0.9% (5%) PERJETA 3 PERJETA (pertuzumab) 420 mg/14 ml (30 mg/ml) 4 pertuzumab 5 5.1-3

PERJETA (cynomolgus monkey) pertuzumab - PERJETA [ (8.1)] PERJETA - PERJETA PERJETA 5.2 (Left ventricular dysfunction) HER2 ( PERJETA ) CLEOPATRA Herceptin docetaxel PERJETA Herceptin docetaxel (LVD [ ]) (LVEF) [ (13.1)] PERJETA 6.6 8.6% PERJETA ( ) 1.5% 1.8% [ (6.1)] anthracyclines (NEOSPHERE) trastuzumab docetaxel PERJETA (LVD) PERJETA trastuzumab docetaxel (LVEF) LVEF 50% NEOSPHERE ( 2) 4 PERJETA (LVD) PERJETA Herceptin docetaxel (7.5%) Herceptin docetaxel (1.9%) PERJETA Herceptin LVD TRYPHAENA LVD PERJETA Herceptin FEC PERJETA Herceptin docetaxel 8.3% FEC PERJETA Herceptin docetaxel 9.3% PERJETA TCH 6.6% LVD ( ) FEC PERJETA Herceptin docetaxel 1.3% ( FEC PERJETA Herceptin docetaxel LVD ) PERJETA TCH 1.3% PERJETA Herceptin FEC PERJETA Herceptin docetaxel LVD PERJETA 50% (CHF) Herceptin < 50% 4

anthracycline > 360 mg/m 2 doxorubicin PERJETA ( ) < 45% 45% - 49% 10% PERJETA Herceptin 3 PERJETA Herceptin [ (2.2)] 5.3 PERJETA [ (6.1)] III CLEOPATRA (anaphylactic reaction) PERJETA Herceptin docetaxel PERJETA PERJETA PERJETA 13.2% 9.8% 1% 3-4 ( 1.0%) PERJETA ( 1.0%) 2 (NEOSPHERE) 3 (TRYPHAENA) PERJETA 1 (CLEOPATRA) (NCI - CTCAE 3.0 ) 1 2 PERJETA 60 30 [ (2.2)] 5.4 / 1 (CLEOPATRA) PERJETA / 11.3% 9.3% (NCI-CTCAE) 3.0 PERJETA 3-4 / 2% 2.5% PERJETA 4 2 2 (NEOSPHERE) 3 (TRYPHAENA) / 1 (CLEOPATRA) 2 (NEOSPHERE) 2 PERJETA docetaxel 3 (TRYPHAENA) / PERJETA TCH (13.2%) 2.6% NCI-CTCAE ( 3.0 ) 3 4 5

PERJETA [ (6.1)] PERJETA PERJETA [ (4)] 5.5 HER2 HER2 PERJETA [ (1) (13)] HER2 Dako Herceptest IHC 3+ Dako HER2 FISH PharmDx (FISH) 2.0 FISH IHC HER2 ( ) 6 - [ (5.1)] [ (5.2)] [ (5.3)] / [ (5.4)] 6.1 PERJETA 1600 CLEOPATRA (n=808) NEOSPHERE (n=417) TRYPHAENA (n=225) I II PERJETA I II PERJETA CLEOPATRA NEOSPHERE TRYPHAENA (ADRs) pertuzumab (metastatic breast cancer, MBC) CLEOPATRA PERJETA Herceptin docetaxel (ADRs) ( 50%) (NCI-CTCAE) ( 3.0 ) 3 4 (ADRs) ( 10%) 6

docetaxel PERJETA Herceptin (28.1%) (18.3%) (18.3%) (17.0%) (17.0%) (13.7%) (13.4%) (13.4%) (12.7%) (11.4%) 10% (<10%) NEOSPHERE PERJETA Herceptin docetaxel ( 50%) NCI-CTCAE ( 3.0 ) 3 4 ( 10%) TRYPHAENA FEC 3 PERJETA Herceptin docetaxel 3 ( 50%) NCI-CTCAE ( 3 ) 3 4 ( 10%) PERJETA docetaxel carboplatin Herceptin (TCH) 6 ( 50%) NCI-CTCAE ( 3 ) 3 4 (ADR) ( 10%) 1 CLEOPATRA PERJETA Herceptin docetaxel (MBC) NEOSPHERE TRYPHAENA PERJETA Herceptin PERJETA Herceptin 1/10 1/100 <1/10 1/1,000 <1/100 ( 1/10,000 <1/1,000) (<1/10,000) 1 - PERJETA ^ ( [MedDRA] ) PERJETA + Herceptin + ^ ^ n = 980^ ^ ^ (100%) % 7

Product Information % 3 4 % 45.2 41.2 17.1 3.1 14.2 9.7 * 10.7 10.4 ** 4.5 0.8 ** 0.3 0.2 9.0-58.9 6.6 39.5 0.7 23.4 1.3 15.2 0.2 12.3-31.5 1.4 21.5 0.9 8

18.6 1.7 15.6 0.5 12.4 0.2 5.2 0.9 3.1 0.4 11.7 0.3 10.8-3.8-19.6 0.7 18.6 0.6 13.2 0.1 19.3 0.7 14.1-11.6 1.1 9.9 0.4 8.9 0.3 9

Product Information 12.2-9.8 0.7 2.2 0.1 51.0-27.1 0.6 13.5 0.5 9.2-7.7 - ^ 1 CLEOPATRA ( 2014 2 11 PERJETA 24) NEOSPHERE ( PERJETA 4) TRYPHAENA ( PERJETA FEC/Ptz+T+D 3 Ptz+T+FEC/Ptz+T+D Ptz+TCH 6) ^ ^ NEOSPHERE 108 PERJETA + Herceptin docetaxel 94 PERJETA + docetaxel Herceptin ^ ^ ^ CLEOPATRA 45 PERJETA PERJETA 980 * ** MedDRA 10

6.2 PERJETA Product Information PERJETA PERJETA 2.8% (11/386) 6.2% (23/372) PERJETA 34 (ATA) / (anaphylactic/hypersensitivity reactions) ATA PERJETA PERJETA Herceptin PERJETA PERJETA 7 pertuzumab trastuzumab pertuzumab docetaxel 8 8.1 D PERJETA PERJETA PERJETA (trimester) (cynomolgus monkey) pertuzumab (C max ) 2.5 20 - PERJETA PERJETA 19 30-150 mg/kg pertuzumab 2 10-100 mg/kg C max 2.5-20 Pertuzumab 19 50 ( ) 25 70 2 10 30 100 mg/kg pertuzumab ( C max 2.5-20 ) - 33 50 85% 100 pertuzumab pertuzumab 100 29% - 40% 8.3 11

Product Information PERJETA IgG PERJETA PERJETA [ (5.1) (11.2)] 8.4 PERJETA 18 8.5 PERJETA 402 60 (15%) 65 5 (1%) 75 PERJETA < 65 (n = 306) 65 (n = 175) pertuzumab 8.6 PERJETA - PERJETA PERJETA 6 8.7 ( [CLcr] 60-90 ml/min) (CLcr 30-60 ml/min) PERJETA (CLcr 30 ml/min) [ (11.2)] 8.8 pertuzumab 9 PERJETA 10 Pertuzumab (HER2) ( II) Pertuzumab (DNA) ( ) gentamicin gentamicin Pertuzumab 148 kda PERJETA 420 mg pertuzumab 30 mg/ml L-histidine Glacial Acetic Acid Sucrose Polysorbate 20 11 11.1 Pertuzumab (HER2) ( II) HER2 (HER) ( 12

EGFR HER3 HER4) (ligand-dependent heterodimerization) pertuzumab [ (Mitogen-activated protein, MAP) 3 (phosphoinositide 3-kinase, PI3K)] (ligand-initiated intracellular signaling) pertuzumab (antibody-dependent cell-mediated cytotoxicity, ADCC) pertuzumab pertuzumab trastuzumab HER2 11.2 Pertuzumab 2-25 mg/kg ( 481 ) pertuzumab (CL) 0.24 L/day 18 840 mg 3 420 mg pertuzumab ( ) (baseline serum albumin) (lean body weight) 37 pertuzumab trastuzumab pertuzumab docetaxel PERJETA (CLcr 60-90 ml/min n = 200) (CLcr 30-60 ml/min n = 71) pertuzumab (CLcr 90 ml/min n = 200) CLcr (27-244 ml/min) CLcr pertuzumab 11.3 20 HER2 840 mg 3 420 mg pertuzumab QTc Fridericia QT ( 20 ms) QTc ( 10 ms) 12 12.1 pertuzumab pertuzumab pertuzumab pertuzumab 6 13 13.1 13

808 HER2 HER2 IHC 3+ FISH 2.0 1:1 Herceptin docetaxel PERJETA Herceptin docetaxel ( / HER2 ) ( ) 12 (disease free interval) PERJETA 840 mg 3 420 mg Herceptin 8 mg/kg 3 6 mg/kg PERJETA Herceptin Docetaxel 75 mg/m 2 3 6 docetaxel 100 mg/m 2 16.2 PERJETA 19.9 (IRF) (PFS) PFS 18 ( ) (OS) PFS ( ) (ORR) 54 ( 22-89 ) 59% 32% 4% 2 17% 14% 38% 31% ( 48% 50%) (78%) (22%) HER2 192 (47.3%) PERJETA 184 (45.8 %) 45% 11% 11% Herceptin CLEOPATRA IRF PFS PERJETA [ (HR)= 0.62 95% (CI) 0.51, 0.75 p < 0.0001] PFS 6.1 (PERJETA PFS 18.5 12.4 ) ( 1) PFS IRF PFS ( 2) (< 65 65 ) / HER2 ( ) / Herceptin ( ) ( 2) (n = 408) 0.55 (95% CI 0.42, 0.72) (n = 388) 0.72 (95% CI 0.55, 0.95) (n = 178) 0.96 (95% CI 0.61, 1.52) CLEOPATRA 2 : 14

2 CLEOPATRA Product Information : ( ) + trastuzumab + docetaxel n=406 PERJETA + trastuzumab + docetaxel n=402 (95% ) p ( ) : ( ) 242 (59.6%) 12.4 191 (47.5%) 18.5 0.62 [0.51, 0.75] < 0.0001 * ( ) : ( ) 221(54.4%) 40.8 168 (41.8%) 56.5 0.68 [0.56; 0.84] 0.0002 ( ) : (ORR) ** 95% (CR) (PR) (SD) (PD) 250 (61.6%) 12.4 336 233 (69.3%) [64.1, 74.2] 14 (4.2%) 219 (65.2%) 70 (20.8%) 28 (8.3%) 201 (50.0%) 18.5 343 275 (80.2%) [75.6; 84.3] 19 (5.5%) 256 (74.6%) 50 (14.6%) 13 (3.8%) 0.65 [0.56; 0.84] : 10.8% [4.2; 17.5]% < 0.0001 0.0011 ^ ( ) 95% 233 54.1 [46, 64] 275 87.6 [71, 106] * 2014 2 11 ** (RECIST) CR PR ^ (CR) (PR) TRF 15

Product Information 1 IRF Kaplan-Meier D= docetaxel; HR= hazard ratio; Ptz= pertuzumab (PERJETA); T=trastuzumab (Herceptin); 2 (IRF) (PFS) 16

Product Information (OS) PERJETA (OS) PERJETA (OS) ( [Log-Rank] (HR) 0.66 p = 0.0008) 37.6 PERJETA (OS) 389 ( 221 168 ) (OS) PERJETA ( (HR) 0.68 p = 0.0002) 40.8 PERJETA 56.5 ( 2 3) 3 Kaplan-Meier 17

Product Information D= docetaxel; HR= hazard ratio; Ptz= pertuzumab (PERJETA); T=trastuzumab (Herceptin); 13.2 2 (NEOSPHERE) 2 (NEOSPHERE) 417 HER2 (T2-4d) HER2 (IHC) 3 + (ISH) 2.0 4 1 Herceptin docetaxel PERJETA Herceptin docetaxel PERJETA Herceptin PERJETA docetaxel ( ) (ER) (PgR) PERJETA 840 mg 3 420 mg 4 Herceptin 8 mg/kg 3 6 mg/kg 4 3 5-fluorouracil (600 mg/m 2 ) epirubicin (90 mg/m 2 ) cyclophosphamide (600 mg/m 2 ) (FEC) 3 3 Herceptin 1 PERJETA Herceptin FEC docetaxel 3 4 Herceptin 18

(pcr) (ypt0/is) ( T2-3) (DFS) PFS pcr (ypt0/isn0 ypt0n0) ( 49-50 (71%)) 7% 32% 61% ( ER / PgR ) 4 Herceptin docetaxel PERJETA Herceptin docetaxel pcr (ypt0/is) (45.8% 29.0% p = 0.0141) pcr PERJETA (pcr) ( 5.9% 26.0% 27.3% 63.2%) 3 (TRYPHAENA) TRYPHAENA 225 HER-2 (T2-4d) HER2 IHC 3+ ISH 2.0 3 3 FEC 3 docetaxel PERJETA Herceptin 3 FEC 3 PERJETA docetaxel Herceptin 6 PERJETA docetaxel carboplatin Herceptin (TCH) ( ) (ER) (PgR) PERJETA 840 mg 3 420 mg Herceptin 8 mg/kg 3 6 mg/kg 5-Fluorouracil (500 mg/m 2 ) epirubicin (100 mg/m 2 ) cyclophosphamide (600 mg/m 2 ) 3 3 Docetaxel 75 mg/m 2 3 100 mg/m 2 PERJETA TCH docetaxel 75 mg/m 2 carboplatin (AUC 6) 3 6 Herceptin 1 (Herceptin 3 ) pcr (ypt0/is) DFS PFS OS ( 49-50 (77%) 6% 25% 69% ER / PgR 19

3 pcr ( 3) pcr pcr ( 46.2% 50.0% 65.0% 83.8%) 3 : NEOSPHERE (WO20697) TRYPHAENA (BO22280) ( ) T+D N=107 NEOSPHERE (WO20697) Ptz+T+D N=107 ypt0/is (%) [95% ] 1 31 (29.0%) [20.6; 38.5] 49 (45.8%) [36.1; 55.7] PCR 2 +16.8 % [95% ] 3 [3.5; 30.1] p (CMH Simes ) 4 0.0141 (vs. T+D) ypt0/is N0 (%) [95% ] ypt0 N0 (%) [95% ] 23 (21.5%) [14.1; 30.5] 13 (12.1%) [6.6; 19.9] 5 79 (79.8%) 42 (39.3%) [30.3; 49.2] 35 (32.7%) [24.0; 42.5] 89 (88.1%) Ptz+T N=107 18 (16.8%) [10.3; 25.3] Ptz+D N=96 23 (24.0%) [15.8; 33.7] -12.2 % -21.8 % [-23.8; -0.5] [-35.1; -8.5] 0.0198 (vs. T+D) 12 (11.2%) [5.9; 18.8] 6 (5.6%) [2.1; 11.8] 69 (67.6%) 0.0030 (vs Ptz+T+D) 17 (17.7%) [10.7; 26.8] 13 (13.2%) [7.4; 22.0] TRYPHAENA (BO22280) Ptz+T+FEC/ Ptz+T+D N=73 45 (61.6%) [49.5; 72.8] FEC/ Ptz+T+D N=75 43 (57.3%) [45.4; 68.7] Ptz+TCH N=77 51 (66.2%) [54.6; 76.6] NA NA NA NA NA NA 41 (56.2%) [44.1; 67.8] 37 (50.7%) [38.7; 62.6] 65 (71.4%) 67 (91.8%) 41 (54.7%) [42.7; 66.2] 34 (45.3%) [33.8; 57.3] 71 (94.7%) 49 (63.6%) [51.9; 74.3] 40 (51.9%) [40.3; 63.5] 69 (89.6%) ( 3) T: Herceptin D: docetaxel Ptz: FEC: 5-fluorouracil epirubicin cyclophosphamide TCH: docetaxel carboplatin trastuzumab 1. 95% Pearson-Clopper 2. Ptz+T+D Ptz+T T+D Ptz+D Ptz+T+D 3. 95% Hauck-Anderson 4. p Cochran-Mantel-Haenszel Simes 20

Product Information 5. CR PR ( ) 14 / 14.1 PERJETA 420 mg/14 ml (30 mg/ml) 2 C-8 C (36 F-46 F) 15 PERJETA - [ (5.1) (8.1)] PERJETA PERJETA 6 [ (5.1) (8.6)] PERJETA PERJETA [ (8.3)] 14 100 2015 08 CDS 5.0_US PI 12.15-PER-3B02 Roche Diagnostics GmbH Sandhofer Strasse 116, D-68305 Mannheim, Germany F. Hoffmann-La Roche Ltd. Wurmisweg, CH-4303 Kaiseraugst, Switzerland. 3 134 9 (02)27153111 21