Slide 1: Results from VELOUR, a Phase 3 Study of Aflibercept Plus FOLFIRI
Results from VELOUR, a Phase 3 Study Of Aflibercept Versus Placebo In Combination With FOLFIRI For The Treatment Of Patients With Previously Treated Metastatic Colorectal Cancer Results from Prespecified Subgroup Analyses Josep Tabernero*, E. Van Cutsem, R. Lakomy, J. Prausova, P. Ruff, G. Van Hazel
Slide 2: Aflibercept: fusion protein of key domains from VEGF receptors
Fusion protein of key domains from human VEGF receptors 1 and 2 with human IgG Fe" Blocks all human VEGF-A isoforms, VEGF-B and placental growth factor (PIGFY High affinity—binds VEGF-A and PIGF more tightly than native receptors Contains human amino acid sequences’ {Ape om Hh roc ata 5 20098:1309-1
Slide 3: VELOUR Study Design
VELOUR Study Design Stratification factors: -ECOG PS (0 vs 1 vs 2) - Prior bevacizumab (Y/N) Aflibercept 4 mg/kg IV, day 1 + FOLFIRI q2 weeks 2 BY I n i Placebo IV, day 1 MN-ZOOZ>DA V3 + FOLFIRI q2 weeks Primary endpoint: Overall survival Sample size determination: Sized to demonstrate a HR of 0.8 w
Slide 4: Overall Survival, ITT Population
Overall Survival, ITT Population 1.0 09 os o7 06 os oa 03 Kaplan-Meier Estimate 02 o4 0.0 ‘Symbol=Censor Placebo/FOLFIRI = = Median = 12.06 months AflibercepUFOLFIRI = -=--2 Median = 13.50 months Stratified HR=0.817 [95.34%CI, 0.713.0.937] Log-rank p= 0.0032 Onn Number at Risk Placebo 614 573 AFLL 6
Slide 5: Secondary Endpoints
Secondary Endpoints. Progression Free Survival Overall Response Rate ITT Population Evaluable Population ‘Symbal=Censor PhcabiFOLERL == Maen = 467 mots AMaacgAFOLERL “© Man = 680 ots : eee Saari Placebo _Aflibercept i N=530 N=531 je ORR(%) 14.1 19.8 i 95%Cl 850138 16.4t023.2 x! . p= 0.0001 a i. a a
Slide 6: Pre-specified Subgroup Analyses
Pre-specified Subgroup Analyses * Goal: to confirm consistency of the effect of aflibercept on OS and PFS * Methodology: impact assessment on pre- specified subgroups: — Stratification factors + ECOG PS, Prior bevacizumab — Baseline characteristics + Age, gender, geographic region + Prior hypertensi
Slide 7: Cox Proportional Hazard Model methodology for subgroups
For each parameter, a Cox Proportional Hazard Model was used for overall lation, including the parameter, the treatment effect the treatment by parameter interaction. Interactions between treatment and each subgroup were tested at the 2-sided 10% level a — ie, a p-value > 0.1 inglegie sino vidence e
Slide 8: Overall Survival by Stratification Factors
Overall Survival by Stratification Factors — ITT Population Strata (as perIVRS) N= — HR[95.34%Cl] Favors Aflibercept Favors Placebo P-values of interaction All pationts 1226 0.817 (0.7130 0.937) ~ ECOG PS=0 699 0,768 (0.635 t0 0.928) ECOG PS=1 500 0.869 (0.71 to 1.063) ECOG PS=2 270.978 (0.43 02.221
Slide 9: Overall Survival by Demographic Characteristics
Overall Survival by Demographic Characteristics — ITT Population Subgroups —-N=_-HR [95.34% Cl] Favors Afibercept Favors Placebo Allpatients 1226 0.817 (0.713 to 0.937) ed P-values of interaction Age <65 783 0.796 (0.67 to 0.945) =o Jaro Age >=65 443 0,853 (0.682 to 1.066) oe} Mate 718 0.83 (0.696 t
Slide 10: Overall Survival by Baseline Characteristics
Overall Survival by Baseline Characteristics — ITT Population Subgroups N= HR 95.34% Cl] Favors Aflibercept | Favors Placebo All patients 1226 0.817 (0.71310 0.937) oe P-values of interaction No prior hypertension 6920.83 (0.74 to 1.054) _ oe Prior hypertension 534 0.714 (0.577 to 0.884) Number of o
Slide 11: Progression Free Survival by Stratification Factors
Progression Free Survival by Stratification Factors — ITT Population Strata(asperIVRS) N= HR [95% Ci] Favors Aflibercept Favors Placebo Ail patients 1226 0.758 (0.664 to 0.869) ao Seu : interaction ECOG FS=0 699 0.764 (0.633 to 0.913) — ECOG PS: ECOG PS=1 500 0.749 (0.607 to 0.923) + ara ECoG PS=2 2
Slide 12: Progression Free Survival by Demographic Characteristics
sion Free Survival by Demographic Characteristics — ITT Population Subgroups -N=_-HR195% Cl] Favors Aflibercept Favors Placebo Allpationts 1226. (0.758 (0.661 to 0.869) ~— P.values of interaction Age <65 783. 0,765 (0.645 to 0.909) — Ages Age >=65 443 0.748 (0.598 to 0.936) — Mate 718 0,709(0,045 10
Slide 13: Progression Free Survival by Baseline Characteristics
sion Free Survival by Baseline Characteristics — ITT Population Subgroups N= HR [95% Cl] Favors Aflibercept | Favors Placebo All patients 1226 0.758 (0.661 to 0.869) x P-values of interaction No prior hypertension 6820.76 (0.616 to 0.88) <= Prix fopertension: p=0 788 Prior hypertension 534 0.764 (0.
Slide 14: Prior Treatment with Bevacizumab
No Prior Treatment with Bevacizumab Number of Patients Placebo/FOLFIRI Aflibercept/FOLFIRI N=614 N= 612 Yes 187 (30.5%) 186 (30.4) 427 (69.5%) 426 (69.6%)
Slide 15: Overall Survival: Patients with or without Prior Bevacizumab
Overall Survival: Patients with or without Prior Treatment with Bevacizumab - ITT Population Placebo/ FOLFIRI —Aflibercept/FOLFIRI P-value for Median (mos) Median (mos) interaction N=614 N=612 All Patients 12.1 13.5 All Patients Prior BEV No 12.4 13.9 0.7231 Yes 11.7 12.5 Interaction between “treatm
Slide 16: Overall Survival, Patients with Prior Bevacizumab
Overall Survival, Patients with Prior Treatment with Bevacizumab - ITT Population ‘Symbol=Censor Placebo/FOLFIRI =—=—= Median = 11.7 months Aflibercept/FOLFIRI =--2--> Median = 12.5 months 1.0 0.9 0.8 HR: 0.862 [95.34%CI: 0.673-1.104] 0.7 0.6 05 0.4 0.3 0.2 0.1 0.0 o 3 6 9 12 15 18 21 24 27 30 33 36
Slide 17: Progression Free Survival by Prior Bevacizumab Treatment
Treatment with Bevacizumab - ITT Placebo/ FOLFIRI Aflibercept/FOLFIRI P value for Median (mos) Median (mos) interaction N=614 N=612 All Patients 47 69 Prior BEV No 5A 69 Yes 3.9 67 . Interaction between “treatment arm” and “prior bevacizumab” factor was Not significant at the 2-sided 10% level (p =
Slide 18: Progression Free Survival, Patients with Prior Bevacizumab
Progression Free Survival, Patients with Prior Treatment with Bevacizumab - ITT Population 1.04. Symbol=Censor Placebo/FOLFIRI =—>—> Median = 3.9 months 09 AfliberceptFOLFIRI >->--2 Median = 6.7 months 0.8: 0.7, a HR: 0.661 [95%CI: 0.512-0.852] 0.5 04 *, 0.3: 0.2 0.1 OO OS 612 8 at 2a 2730 Number at
Slide 19: Safety — Anti-VEGF Associated Events
Safety — Anti-VEGF Associated Events Overall Population eerie % of Placebo/FOLFIRI Aflibercept/FOLFIRI N= 605 N=611 Grouped Term, AllGrade Grade 3/4__AllGrade__Grade 3/4 Proteinuria” 40.7 12 62.2 79 Hypertension 10.7 1.5 aA 19.3 Haemorrhage 19.0 17 37.8 29 Biase TA 0 27.7 0.2 origin 54 1.0 10.0 2.0
Slide 20: Safety — Anti-VEGF Events by Prior Bevacizumab
Safety — Anti-VEGF Associated Events By Prior Treatment with Bevacizumab Patients Receiving Aflibercept See eetcn faci Spuies eg prams) Lica ep ease poet AllGrade Grade 3/4__AllGrade _Grade 3/4 62.5 61.5 Hypertension 222 205 396 19.9 Haemorrhage 37.3 28 39.0 3.2 Epistaxis 264 02 305 0 Glorigin 99 17
Slide 21: Conclusions
Conclusions Adding aflibercept to FOLFIRI in mCRC patients previously treated with oxaliplatin based regimen resulted in OS and PFS benefits that are both statistically significant and clinically meaningful smo/wccc 2011, Barcelona, Abstract 0-0024) : - OS: HR=0.817 [95.34%Cl, 0.713-0.937], p = 0.00
Slide 22: Acknowledgements
Acknowledgements
Slide 23: Acknowledgements
Acknowledgements Ee atte es ie lt i tigi bo arco Seams ine being developed in oncology in a Robin E + Fehrenbacher L partnership between Regeneron Unite States (cont) = ard * couse R 2 Aline * Chara * Polka J "Van Vethzen “Vnil A “Thomas Gras * Congr > hon T * Geis eG Guarino M = Vindavnam Ny Fee oe