ARIEL3: A PHASE 3, RANDOMISED, DOUBLE-BLINDSTUDY OF RUCAPARIB VS PLACEBO FOLLOWINGRESPONSE TO PLATINUM-BASED CHEMOTHERAPYFOR RECURRENT OVARIAN CARCINOMA (OC)Jonathan A. Ledermann,1 Amit M. Oza,2 Domenica Lorusso,3 Carol Aghajanian,4 Ana Oaknin,5 Andrew Dean,6Nicoletta Colombo,7 Johanne I. Weberpals,8 Andrew Clamp,9 Giovanni Scambia,10 Alexandra Leary,11

Robert W. Holloway,12 David M. O’Malley,13 Terri Cameron,14 Lara Maloney,14 Sandra Goble,14 Kevin Lin,14

James Sun,15 Heidi Giordano,14 Robert L. Coleman16

1UCL Cancer Institute and UCL Hospitals, London, UK; 2Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; 3Fondazione IRCCS Istituto Nazionale dei Tumori and MITO, Milan, Italy; 4Memorial Sloan Kettering Cancer Center, New York, NY, USA; 5Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain; 6Saint John of God SubiacoHospital, Subiaco, WA, Australia; 7European Institute of Oncology and University of Milan-Bicocca, Milan, Italy; 8Ottawa Hospital Research Institute, Ottawa, ON, Canada; 9The Christie NHS Foundation Trust and University of Manchester, Manchester, UK; 10Università Cattolica Roma, Rome, Italy; 11Gustave Roussy Cancer Center, INSERM U981, and Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens (GINECO), Villejuif, France; 12Florida Hospital Cancer Institute, Orlando, FL, USA; 13The Ohio State University, James Cancer Center, Columbus, OH, USA; 14Clovis Oncology, Inc., Boulder, CO, USA; 15Foundation Medicine, Inc., Cambridge, MA, USA; 16The University of Texas MD Anderson Cancer Center, Houston, TX, USA

All ARIEL3 study patients and their families and caregiversRobert L. Coleman, The University of Texas MD Anderson Cancer Center, Houston, TX – Co-coordinating investigator for ARIEL3Additional ARIEL3 investigators and sites: M. Amenedo Gancedo (Centro Oncológico Regional de Galicia), P. C. Fong (Auckland City Hospital), J. C. Goh (Royal Brisbane and Women's Hospital), D. K. Armstrong (The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins), S. N. Banerjee (Royal Marsden Hospital), J. Garcia-Donas (HM Centro Integral Oncológico Clara Campal), E. M. Swisher (University of Washington), A. Floquet (Institut Bergonié), I. A. McNeish (Beatson Cancer Centre Glasgow), C. L. Scott (Peter MacCallum Cancer Centre - Melbourne), Lm. Chen (University of California San Francisco), A. Lortholary (Centre Catherine de Sienne), R. T. Morris (Karmanos Cancer Institute), O. Tredan (Centre Léon Bérard), B. You (Centre Hospitalier Lyon Sud), P. Harnett (Westmead Hospital), J. Medioni (Hôpital EuropéenGeorges-Pompidou), C. Parkinson (Addenbrooke's Hospital), D. Provencher (Centre Hospitalier de L'Université de Montréal), L. Elit (Juravinski Cancer Centre), P. Ghatage(Tom Baker Cancer Center), G. E. Konecny (University of California Los Angeles), S. Pignata (Istituto Nazionale Tumori IRCCS Fondazione Pascale), I. Vergote (UniversitairZiekenhuis Leuven), S. Welch (London Regional Cancer Centre), H. Denys (Universitair Ziekenhuis Gent), M. Leviov (The Lady Davis Carmel Medical Center), M. Plante(Centre Hospitalier Universitaire de Quebec), A. Amit (Rambam Medical Center), M. J. Birrer (Massachusetts General Hospital), A. Casado Herraez (Hospital San Carlos Madrid), S. K. Chambers (University of Arizona Cancer Center), M. L. Friedlander (Prince of Wales Hospital), E. Guerra (Hospital Ramón y Cajal), M. A. Morgan (University of Pennsylvania), R. F. Sabbatini (Azienda Ospedaliero-Universitaria di Modena - Policlinico), R. Shapira-Frommer (Chaim Sheba Medical Center at Tel Hashomer), S. Tamberi(Ospedale Civile degli Infermi), P. Wimberger (Technische Universität Dresden), M. Buck (Sir Charles Gairdner Hospital), L. Dirix (AZ Sint Augustinus), L. Gladieff (InstitutClaudius Régaud), D. Jackson (Saint James's University Hospital), G. Kichenadasse (Flinders Medical Centre), L. Ma (Rocky Mountain Cancer Centers), C. Zamagni(Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi), M. K. Buss (Beth Israel Deaconess Medical Center), H. G. S. Gabra (Imperial College Healthcare NHS Trust), S. Kovel (Assaf Harofeh Medical Centre), P. Krabisch (Klinikum Chemnitz gGmbH), J. Lotz (Hôpital Tenon), T. Neunhöffer (HELIOS Dr. Horst Schmidt Kliniken Wiesbaden - Klinik für Gynäkologie und Gyn. Onkologie), A. O'Donnell (Wellington Regional Hospital), M. Powell (Barts and The London NHS Trust), I. Romero (Instituto Valenciano de Oncología-Fundación [IVO-FINCIVO]), T. Safra (Tel Aviv Sourasky Medical Center), A. Sanchez (Hospital Regional Universitario de Málaga Hospital General), S. Stemmer (Rabin Medical Center), T. Vanderkwaak (Hope Women’s Cancer Centers), A. Bologna (Arcispedale Santa Maria Nuova), Y. Drew (Freeman Hospital - Northern Centre for Cancer Care), A. El-Balat (Universitätsklinikum Frankfurt), C. Hänle (Klinikum Ludwigsburg-Bietigheim gGmbH), F. Joly (Centre de Lutte contre le Cancer François Baclesse), D. G. Mutch (Washington University School of Medicine), I. Palacio (Hospital Universitario Central de Asturias), M. Pölcher(Rotkreuzklinikum München-Frauenklinik), B. M. Slomovitz (Sylvester Comprehensive Cancer Center), M. Vulfovich (Memorial Healthcare System)

2

ACKNOWLEDGEMENTS

Medical writing and editorial support funded by Clovis Oncology were provided by Nathan Yardley, PhD, and Shannon Davis of Ashfield Healthcare Communications.

• Prof. Jonathan A. Ledermann has:• Served in an advisory role for Clovis Oncology, AstraZeneca, Roche, and Pfizer• Served on a speakers bureau for AstraZeneca and Pfizer• Received research grants from AstraZeneca

3

DISCLOSURES

• Rucaparib is a potent inhibitor of PARP1, PARP2, and PARP31,2

• Rucaparib has shown antitumour activity in patients with recurrent OC3,4 whose tumour harbours one of the following:

• A BRCA mutation• High percentage of genomic LOH, a phenotypic marker of HRD

• Rucaparib is approved in the United States for the treatment of patients with deleterious BRCA mutation (germline or somatic) associated advanced OC who have been treated with ≥2 chemotherapy regimens5

The ARIEL3 phase 3 trial evaluated rucaparib vs placebo following a response to second-line or later platinum-based chemotherapy in patients with high-grade, recurrent platinum-sensitive OC, including fallopian tube and primary peritoneal carcinomasLOH, loss of heterozygosity; PARP, poly(ADP-ribose) polymerase.1. 2. Thomas HD et al. Mol Cancer Ther. 2007;6:945-56; 3. Kristeleit R et al. Clin Cancer Res. 2017; 23:4095-106;

Swisher EM et al. Rucaparib tablets [prescribing information]. Boulder, CO: Clovis Oncology, Inc.; 2017.Robillard et al. Cancer Res. 2017;77(13 suppl):abstr 2475.;

4. Lancet Oncol. 2017;18:75-87; 5.

4

BACKGROUND

*CR (defined by RECIST v1.1) or PR (defined by RECIST v1.1 and/or a GCIG CA-125 response [CA-125 within normal range]) maintained until entry to ARIEL3 (≤8 weeks of last dose of chemotherapy). † , , , , , , , , , , , , , , , , , , , , ,

, , , , , , HRR, homologous recombination repair; NGS, next-generation sequencing

ATM ATR ATRX BARD1 BLM BRIP1 CHEK1 CHEK2 FANCA FANCC FANCD2 FANCE FANCF FANCG FANCI FANCL FANCM MRE11A NBN PALB2 RAD50RAD51 RAD51B RAD51C RAD51D RAD52 RAD54L RPA1.

.

5

ARIEL3: STUDY DESIGN

• HRR status by NGS mutation analysis BRCA1 or BRCA2 Non-BRCA HRR gene†

None of the above• Response to recent platinum

CR PR

• Progression-free interval after penultimate platinum 6 to <12 months ≥12 months

Patient eligibility Stratification

• High-grade serous or endometrioid epithelial OC, primary peritoneal, or fallopian tube cancers

• Sensitive to penultimate platinum• Responding to most recent platinum

(CR or PR)* Excludes patients without assessable

disease following second surgery• CA-125 within normal range• No restriction on size of residual tumour• ECOG PS ≤1• No prior PARP inhibitors

PlaceboBID

n=189

Rucaparib 600 mg BID

n=375

Ran

dom

isat

ion

2:1

• Primary endpoint: • Investigator-assessed PFS (per RECIST)

•

BRCA mutation and LOH in tumour samples were measured using Foundation Medicine’s T5 NGS assay

*Investigator-assessed PFS at a two-sided 0.05 significance level

Visit cutoff date for all analyses: 15 April 2017.HRD, homologous recombination deficient; ITT, intent to treat.

6

ARIEL3: PRIMARY ENDPOINT AND STEP-DOWN ANALYSIS

Germline or somatic BRCA mutation

Germline or somaticBRCA mutation

+BRCA wild-type/LOH high

(≥16% genomic LOH prespecified)

Germline or somaticBRCA mutation

+ BRCA wild-type/LOH high

+BRCA wild-type/LOH low

+BRCA wild-type/

LOH indeterminate

If

significant*

BRCA-mutant HRDITT

(all comers)

If

significant*

7

ARIEL3: DIAGRAM OF ANALYSIS COHORTS564 enrolled/randomised

196 BRCA mutant 368 BRCA wild type

No more than 150 patients with a known deleterious germline BRCA mutation were to be enrolled to ensure enough patients with carcinomas associated with a somatic BRCA mutation or wild-type BRCA were enrolled to determine statistical significance between rucaparib and placebo in the HRD cohort and the ITT population. *

†Deleterious BRCA mutation detected by next-generation sequencing of tumour tissue but not by central germline blood test. ‡For LOH high, a cutoff of ≥16% genomic LOH was prespecified for ARIEL3.

8

ARIEL3: DIAGRAM OF ANALYSIS COHORTS

BRCA-mutant cohort (n=196)130 rucaparib 66 placebo

564 enrolled/randomised

196 BRCA mutant 368 BRCA wild type

130 germline BRCA mutant*

56 somatic BRCA mutant†

10 undefined BRCA mutant

No more than 150 patients with a known deleterious germline BRCA mutation were to be enrolled to ensure enough patients with carcinomas associated with a somatic BRCA mutation or wild-type BRCA were enrolled to determine statistical significance between rucaparib and placebo in the HRD cohort and the ITT population. *

†Deleterious BRCA mutation detected by next-generation sequencing of tumour tissue but not by central germline blood test. ‡For LOH high, a cutoff of ≥16% genomic LOH was prespecified for ARIEL3.

9

ARIEL3: DIAGRAM OF ANALYSIS COHORTS

HRD cohort (n=354)130 rucaparib 66 placebo + 106 rucaparib 52 placebo

BRCA-mutant cohort (n=196)130 rucaparib 66 placebo

564 enrolled/randomised

196 BRCA mutant 368 BRCA wild type

158 BRCA wild type/LOH high‡

130 germline BRCA mutant*

56 somatic BRCA mutant†

10 undefined BRCA mutant

No more than 150 patients with a known deleterious germline BRCA mutation were to be enrolled to ensure enough patients with carcinomas associated with a somatic BRCA mutation or wild-type BRCA were enrolled to determine statistical significance between rucaparib and placebo in the HRD cohort and the ITT population. *

†Deleterious BRCA mutation detected by next-generation sequencing of tumour tissue but not by central germline blood test. ‡For LOH high, a cutoff of ≥16% genomic LOH was prespecified for ARIEL3.

10

ARIEL3: DIAGRAM OF ANALYSIS COHORTS

ITT population (n=564)130 rucaparib 66 placebo + 106 rucaparib 52 placebo + 139 rucaparib 71 placebo

HRD cohort (n=354)130 rucaparib 66 placebo + 106 rucaparib 52 placebo

BRCA-mutant cohort (n=196)130 rucaparib 66 placebo

564 enrolled/randomised

196 BRCA mutant 368 BRCA wild type

158 BRCA wild type/LOH high‡

161 BRCA wild type/LOH low

49 BRCA wild type/LOH indeterminate

130 germline BRCA mutant*

56 somatic BRCA mutant†

10 undefined BRCA mutant

No more than 150 patients with a known deleterious germline BRCA mutation were to be enrolled to ensure enough patients with carcinomas associated with a somatic BRCA mutation or wild-type BRCA were enrolled to determine statistical significance between rucaparib and placebo in the HRD cohort and the ITT population. *

†Deleterious BRCA mutation detected by next-generation sequencing of tumour tissue but not by central germline blood test. ‡For LOH high, a cutoff of ≥16% genomic LOH was prespecified for ARIEL3.

Stand-alone secondary endpoint • BICR-assessed PFS (per RECIST)

Select exploratory endpoints • PFS by LOH status in patients with BRCA wild-type OC • ORR in patients with measurable disease at baseline

Other secondary endpoints (to be reported separately) • Patient-reported health outcomes• Overall survival

Visit cutoff date for all analyses: 15 April 2017.BICR, blinded independent central review.

11

ARIEL3: ADDITIONAL ENDPOINTS

Characteristic Rucaparib (n=375) Placebo (n=189)Age

Median (range), years 61.0 (39.0–84.0) 62.0 (36.0–85.0)Diagnosis, % (n)

Epithelial ovarian cancer 83.2 (312) 84.1 (159)*Fallopian tube cancer 8.5 (32) 5.3 (10)Primary peritoneal cancer 8.3 (31) 10.1 (19)

Histology, % (n)Serous 95.2 (357) 94.7 (179)Endometrioid 4.3 (16) 3.7 (7)Mixed 0.3 (1) 1.6 (3)Transitional 0.3 (1) 0 (0)

BRCA and LOH Status, % (n)BRCA mutant 34.7 (130) 34.9 (66)

BRCA1BRCA2GermlineSomaticUndefined†

BRCA wild type 65.3 (245) 65.1 (123)LOH highLOH lowLOH indeterminate‡

Visit cutoff date: 15 April 2017. *One (0.5%) patient had a diagnosis of high-grade serous adenocarcinoma that was fallopian and/or ovarian in origin. †Tumour sample was BRCA mutant by Foundation Medicine’s T5 NGS assay, but a blood sample was not available for central germline testing. ‡Tumour sample was not evaluable for percent of genomic LOH due to low tumour content or low aneuploidy.

12

ARIEL3: BASELINE DEMOGRAPHICS

21.3 (80) 19.6 (37)13.3 (50) 15.3 (29)21.9 (82) 25.4 (48)10.7 (40) 8.5 (16)

2.1 (8) 1.1 (2)

28.3 (106) 27.5 (52)28.5 (107) 28.6 (54)8.5 (32) 9.0 (17)

Characteristic Rucaparib (n=375) Placebo (n=189)ECOG PS

0, % (n) 74.7 (280) 72.0 (136)Number of prior chemotherapy regimens

Median (range) 2 (2–6) 2 (2–6)Number of platinum-based regimens

Median (range) 2 (2–6) 2 (2–5)2, % (n) 62.9 (236) 66.7 (126)≥3, % (n) 37.1 (139) 33.3 (63)

Prior bevacizumab use*Yes, % (n) 22.1 (83) 22.8 (43)

Time to progression with penultimate platinumMedian (range), months 13.8 (5.8–120.0) 14.6 (6.0–238.5)6 to <12 months, % (n) 40.3 (151) 40.2 (76)≥12 months, % (n) 59.7 (224) 59.8 (113)

Response to last platinum CR per RECIST, % (n) 33.6 (126) 33.9 (64)PR per RECIST or serologic response per GCIG CA-125 criteria, % (n) 66.4 (249) 66.1 (125)

Measurable disease at baseline (per investigator)Yes, % (n) 37.6 (141) 34.9 (66)

Bulky disease (any lesion >2 cm) at baseline (per independent radiological review)Yes, % (n) 18.9 (71) 15.3 (29)

Visit cutoff date: 15 April 2017. *Prior treatment with bevacizumab was permitted as part of penultimate or earlier treatment.

13

ARIEL3: BASELINE DEMOGRAPHICS

Visit cutoff date: 15 April 2017.

14

ARIEL3: INVESTIGATOR-ASSESSED PROGRESSION-FREE SURVIVALBRCA mutant

At risk (events)

Rucaparib 130 (0) 93 (23) 63 (46) 35 (58) 15 (64) 3 (67) 0 (67)

Placebo 66 (0) 24 (37) 6 (53) 3 (55) 1 (56) 0 (56)Rucaparib, 48% censored Placebo, 15% censored

Median(months) 95% CI

Rucaparib(n=130)

16.6 13.4–22.9

Placebo(n=66)

5.4 3.4–6.7

HR, 0.23; 95% CI, 0.16–0.34;

P<0.0001

15

ARIEL3: INVESTIGATOR-ASSESSED PROGRESSION-FREE SURVIVALBRCA mutant HRD

Median(months) 95% CI

Rucaparib(n=236)

13.6 10.9–16.2

Placebo(n=118)

5.4 5.1–5.6

HR, 0.32; 95% CI, 0.24–0.42;

P<0.0001

At risk (events)

Rucaparib 130 (0) 93 (23) 63 (46) 35 (58) 15 (64) 3 (67) 0 (67)

Placebo 66 (0) 24 (37) 6 (53) 3 (55) 1 (56) 0 (56)Rucaparib, 48% censored Placebo, 15% censored

At risk (events)

Rucaparib 236 (0) 161 (55) 96 (104) 54 (122) 21 (129) 5 (134) 0 (134)

Placebo 118 (0) 40 (68) 11 (95) 6 (98) 1 (101) 0 (101)Rucaparib, 43% censored Placebo, 14% censored

Median(months) 95% CI

Rucaparib(n=130)

16.6 13.4–22.9

Placebo(n=66)

5.4 3.4–6.7

HR, 0.23; 95% CI, 0.16–0.34;

P<0.0001

Visit cutoff date: 15 April 2017.

16

ARIEL3: INVESTIGATOR-ASSESSED PROGRESSION-FREE SURVIVALBRCA mutant HRD ITT

Median(months) 95% CI

Rucaparib(n=236)

13.6 10.9–16.2

Placebo(n=118)

5.4 5.1–5.6

HR, 0.32; 95% CI, 0.24–0.42;

P<0.0001

Median(months) 95% CI

Rucaparib(n=375)

10.8 8.3–11.4

Placebo(n=189)

5.4 5.3–5.5

HR, 0.36; 95% CI, 0.30–0.45;

P<0.0001

At risk (events)

Rucaparib 130 (0) 93 (23) 63 (46) 35 (58) 15 (64) 3 (67) 0 (67)

Placebo 66 (0) 24 (37) 6 (53) 3 (55) 1 (56) 0 (56)Rucaparib, 48% censored Placebo, 15% censored

At risk (events)

Rucaparib 236 (0) 161 (55) 96 (104) 54 (122) 21 (129) 5 (134) 0 (134)

Placebo 118 (0) 40 (68) 11 (95) 6 (98) 1 (101) 0 (101)Rucaparib, 43% censored Placebo, 14% censored

At risk (events)

Rucaparib 375 (0) 228 (111) 128 (186) 65 (217) 26 (226) 5 (234) 0 (234)

Placebo 189 (0) 63 (114) 13 (160) 7 (164) 2 (167) 1 (167) 0 (167)Rucaparib, 38% censored Placebo, 12% censored

Median(months) 95% CI

Rucaparib(n=130)

16.6 13.4–22.9

Placebo(n=66)

5.4 3.4–6.7

HR, 0.23; 95% CI, 0.16–0.34;

P<0.0001

Visit cutoff date: 15 April 2017.

Visit cutoff date: 15 April 2017. NR, not reached.

17

ARIEL3: BICR-ASSESSED PROGRESSION-FREE SURVIVAL

Median(months) 95% CI

Rucaparib(n=130)

26.8 19.2–NR

Placebo(n=66)

5.4 4.9–8.1

HR, 0.20; 95% CI, 0.13–0.32;

P<0.0001

Median(months) 95% CI

Rucaparib(n=236)

22.9 16.2–NR

Placebo(n=118)

5.5 5.1–7.4

HR, 0.34; 95% CI, 0.24–0.47;

P<0.0001

Median(months) 95% CI

Rucaparib(n=375)

13.7 11.0–19.1

Placebo(n=189)

5.4 5.1–5.5

HR, 0.35; 95% CI, 0.28–0.45;

P<0.0001

BRCA mutant HRD ITT

At risk (events)

Rucaparib 130 (0) 93 (19) 62 (31) 35 (36) 15 (40) 2 (42) 0 (42)

Placebo 66 (0) 18 (34) 6 (39) 2 (42) 1 (42) 0 (42)Rucaparib, 68% censored Placebo, 36% censored

At risk (events)

Rucaparib 236 (0) 152 (49) 87 (78) 53 (84) 21 (88) 4 (90) 0 (90)

Placebo 118 (0) 34 (57) 12 (69) 5 (73) 1 (74) 0 (74)Rucaparib, 62% censored Placebo, 37% censored

At risk (events)

Rucaparib 375 (0) 213 (95) 114 (143) 60 (157) 24 (162) 4 (165) 0 (165)

Placebo 189 (0) 50 (106) 13 (128) 6 (132) 2 (133) 1 (133) 0 (133)Rucaparib, 56% censored Placebo, 30% censored

18

ARIEL3: DIAGRAM OF ANALYSIS COHORTS

ITT population (n=564)130 rucaparib 66 placebo + 106 rucaparib 52 placebo + 139 rucaparib 71 placebo

HRD cohort (n=354)130 rucaparib 66 placebo + 106 rucaparib 52 placebo

BRCA-mutant cohort (n=196)130 rucaparib 66 placebo

564 enrolled/randomised

196 BRCA mutant 368 BRCA wild type

158 BRCA wild type/LOH high‡

161 BRCA wild type/LOH low

49 BRCA wild type/LOH indeterminate

130 germline BRCA mutant*

56 somatic BRCA mutant†

10 undefined BRCA mutant

No more than 150 patients with a known deleterious germline BRCA mutation were to be enrolled to ensure enough patients with carcinomas associated with a somatic BRCA mutation or wild-type BRCA were enrolled to determine statistical significance between rucaparib and placebo in the HRD cohort and the ITT population. *

†Deleterious BRCA mutation detected by next-generation sequencing of tumour tissue but not by central germline blood test. ‡For LOH high, a cutoff of ≥16% genomic LOH was prespecified for ARIEL3.

19

ARIEL3 EXPLORATORY ANALYSIS: INVESTIGATOR-ASSESSEDPROGRESSION-FREE SURVIVAL IN PATIENTS WITH BRCA WILD-TYPE OC

Visit cutoff date: 15 April 2017.

At risk (events)

Rucaparib 106 (0) 68 (32) 33 (58) 19 (64) 6 (65) 2 (67) 0 (67)

Placebo 52 (0) 16 (31) 5 (42) 3 (43) 0 (45)

Rucaparib, 37% censored Placebo, 13% censored

Median(months) 95% CI

Rucaparib(n=106)

9.7 7.9–13.1

Placebo(n=52)

5.4 4.1–5.7

HR, 0.44; 95% CI, 0.29–0.66;

P<0.0001

Median(months) 95% CI

Rucaparib(n=107)

6.7 5.4–9.1

Placebo(n=54)

5.4 5.3–7.4

HR, 0.58; 95% CI, 0.40–0.85;

P=0.0049

LOH high LOH low

At risk (events)

Rucaparib 107 (0) 49 (47) 23 (65) 8 (77) 4 (79) 0 (81)

Placebo 54 (0) 20 (32) 2 (49) 1 (50) 1 (50) 1 (50) 0 (50)

Rucaparib, 24% censored Placebo, 7% censored

20

ARIEL3 EXPLORATORY ANALYSIS: BICR-ASSESSED PROGRESSION-FREESURVIVAL IN PATIENTS WITH BRCA WILD-TYPE OC

Visit cutoff date: 15 April 2017.

At risk (events)

Rucaparib 106 (0) 59 (30) 25 (47) 18 (48) 6 (48) 2 (48) 0 (48)

Placebo 52 (0) 16 (23) 6 (30) 3 (31) 0 (32)

Rucaparib, 55% censored Placebo, 38% censored

Median(months) 95% CI

Rucaparib(n=106)

11.1 8.2–NR

Placebo(n=52)

5.6 2.9–8.2

HR, 0.55; 95% CI, 0.35–0.89;

P=0.0135

Median(months) 95% CI

Rucaparib(n=107)

8.2 5.6–10.1

Placebo(n=54)

5.3 2.8–5.5

HR, 0.47; 95% CI, 0.31–0.71;

P=0.0003

LOH high LOH low

At risk (events)

Rucaparib 107 (0) 46 (37) 20 (55) 6 (61) 3 (62) 0 (63)

Placebo 54 (0) 13 (38) 1 (46) 1 (46) 1 (46) 1 (46) 0 (46)

Rucaparib, 41% censored Placebo, 15% censored

Visit cutoff date: 15 April 2017.*Tumour sample was not evaluable for percent of genomic LOH due to low tumour content or low aneuploidy.

21

ARIEL3: INVESTIGATOR-ASSESSED PFS IN ITT POPULATION SUBGROUPSRucaparib (n) Placebo (n)

All patients 375 189BRCA or LOH Status

BRCA mutantBRCA1 80 37BRCA2 50 29Germline 82 48Somatic 40 16

BRCA wild typeLOH high 106 52LOH low 107 54LOH indeterminate* 32 17

Measurable disease at baseline (per investigator)Yes 141 66No 234 123

Bulky (any lesion >2 cm) disease at baselineYes 71 29No 304 160

Total number of prior platinum regimens2 236 126≥3 139 63

Time to progression on penultimate platinum6 to <12 months 151 76≥12 months 224 113

Response to last platinumCR per RECIST 126 64PR per RECIST or GCIG CA-125 criteria 249 125

HR (95% CI)Favours Rucaparib Favours Placebo

BRCA Mutant HRD ITT

Rucaparib(n=40)

Placebo(n=23)

Rucaparib(n=85)

Placebo(n=41)

Rucaparib(n=141)

Placebo(n=66)

RECIST ORR, % (n) 37.5* (15) 8.7 (2) 27.1* (23) 7.3 (3) 18.4* (26) 7.6 (5)

Complete response 17.5 (7) 0 (0) 11.8 (10) 0 (0) 7.1 (10) 1.5 (1)

Partial response 20.0 (8) 8.7 (2) 15.3 (13) 7.3 (3) 11.3 (16) 6.1 (4)

Stable disease 47.5 (19) 34.8 (8) 50.6 (43) 41.5 (17) 50.4 (71) 43.9 (29)

Progressive disease 12.5 (5) 56.5 (13) 21.2 (18) 51.2 (21) 27.0 (38) 48.5 (32)

Not evaluable 2.5 (1) 0 (0) 1.2 (1) 0 (0) 4.3 (6) 0 (0)

*Cochran-Mantel-Haenszel P<0.05 vs placebo.

Visit cutoff date: 15 April 2017.

22

ARIEL3: EXPLORATORY ANALYSIS: INVESTIGATOR-ASSESSEDORR FOR PATIENTS WITH MEASURABLE DISEASE AT BASELINE

Rucaparib n=372, % (n)* Placebo n=189, % (n)

At least 1 AE 100 (372) 96.3 (182)

At least 1 AE grade ≥3 56.2 (209) 14.8 (28)

Treatment interruption and/or dose reduction due to AE 70.7 (263) 10.6 (20)

Treatment interruption due to AE 63.7 (237) 10.1 (19)

Dose reduction due to AE 54.6 (203) 4.2 (8)

Discontinued due to AE† 13.4 (50) 1.6 (3)

Deaths due to AE 1.6 (6) 1.1 (2)

Deaths due to disease progression 0.5 (2) 0.5 (1)

23

ARIEL3: SUMMARY OF SAFETY

Visit cutoff date: 15 April 2017. *Three patients randomised to the rucaparib arm did not receive a dose of rucaparib and are excluded from the safety population. †Excluding disease progression.AML, acute myeloid leukaemia; MDS, myelodysplastic syndrome.

• Median (range) treatment duration was 8.3 (0.1–34.9) months in the rucaparib arm and 5.5 (0.0–35.4) months in the placebo arm

• MDS/AML were reported in 3 (0.8%) patients in the rucaparib arm and no patients in the placebo arm

Visit cutoff date: 15 April 2017. *Combined terms. †Elevations were transient, self-limiting, and not associated with other signs of liver toxicity. ALT, alanine aminotransferase; AST, aspartate aminotransferase.

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ARIEL3: TREATMENT-EMERGENT ADVERSE EVENTS OF ANY GRADEREPORTED IN ≥15% OF PATIENTS IN EITHER ARM

Rucaparib (n=372) Placebo (n=189)

Incidence (%)

Any gradeGrade ≥3

75.369.4

39.236.636.633.9

31.729.8

23.418.017.215.315.3

36.543.9

6.923.8

14.83.7

21.725.9

13.815.9

0.512.7

1.6

Visit cutoff date: 15 April 2017. *Combined terms. †Elevations were transient, self-limiting, and not associated with other signs of liver toxicity. ALT, alanine aminotransferase; AST, aspartate aminotransferase.

25

ARIEL3: TREATMENT-EMERGENT ADVERSE EVENTS OF ANY GRADEREPORTED IN ≥15% OF PATIENTS IN EITHER ARM

Rucaparib (n=372) Placebo (n=189)

Incidence (%)

Any gradeGrade ≥3

75.3 3.869.4 6.7

39.2 (grade ≥3, 0)36.6 1.936.6 4.033.9 10.5

31.7 0.529.8 2.4

23.4 0.518.0 0.317.2 0.515.3 0.515.3 0.3

0.5 36.52.6 43.9

6.9 (grade ≥3, 0)1.1 23.81.1 14.8

3.7 (grade ≥3, 0)1.1 21.70.5 25.9

13.8 (grade ≥3, 0)0.5 15.90.5 (grade ≥3, 0)

12.7 (grade ≥3, 0)1.6 (grade ≥3, 0)

Visit cutoff date: 15 April 2017. *Combined terms. †Elevations were transient, self-limiting, and not associated with other signs of liver toxicity. ALT, alanine aminotransferase; AST, aspartate aminotransferase.

26

ARIEL3: TREATMENT-EMERGENT ADVERSE EVENTS OF ANY GRADEREPORTED IN ≥15% OF PATIENTS IN EITHER ARM

Rucaparib (n=372) Placebo (n=189)

Incidence (%)

Any gradeGrade ≥3

75.3 3.869.4 6.7

39.2 (grade ≥3, 0)36.6 1.936.6 4.033.9 10.5

31.7 0.529.8 2.4

23.4 0.518.0 0.317.2 0.515.3 0.515.3 0.3

37.428.0

18.0

0.5 36.52.6 43.9

6.9 (grade ≥3, 0)1.1 23.81.1 14.8

3.7 (grade ≥3, 0)1.1 21.70.5 25.9

13.8 (grade ≥3, 0)0.5 15.90.5 (grade ≥3, 0)

12.7 (grade ≥3, 0)1.6 (grade ≥3, 0)

5.82.64.8

75.3 3.869.4 6.7

39.2 (grade ≥3, 0)36.6 1.936.6 4.033.9 10.5

31.7 0.529.8 2.4

23.4 0.518.0 0.317.2 0.515.3 0.515.3 0.3

37.4 18.828.0 5.1

18.0 6.7

0.5 36.52.6 43.9

6.9 (grade ≥3, 0)1.1 23.81.1 14.8

3.7 (grade ≥3, 0)1.1 21.70.5 25.9

13.8 (grade ≥3, 0)0.5 15.90.5 (grade ≥3, 0)

12.7 (grade ≥3, 0)1.6 (grade ≥3, 0)

5.8 (grade ≥3, 0.5)2.6 (grade ≥3, 0)4.8 (grade ≥3, 1.1)

Visit cutoff date: 15 April 2017. *Combined terms. †Elevations were transient, self-limiting, and not associated with other signs of liver toxicity. ALT, alanine aminotransferase; AST, aspartate aminotransferase.

27

ARIEL3: TREATMENT-EMERGENT ADVERSE EVENTS OF ANY GRADEREPORTED IN ≥15% OF PATIENTS IN EITHER ARM

Rucaparib (n=372) Placebo (n=189)

Incidence (%)

Any gradeGrade ≥3

• Rucaparib maintenance treatment significantly improved PFS vs placebo in the nested BRCA-mutant and HRD cohorts and in the overall ITT population

• PFS was improved with rucaparib maintenance treatment vs placebo in patients with BRCA wild-type OC (LOH high and LOH low)

• Several patients with measurable residual disease at baseline had further reduction in tumour burden with rucaparib maintenance treatment

• The most common side effects were gastrointestinal (nausea and vomiting), asthenia, and anaemia, consistent with prior studies of rucaparib

The results of ARIEL3 demonstrate the benefit of rucaparib maintenance treatment for women with platinum-sensitive OC following a complete or partial response to second-line or later platinum-based chemotherapy

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CONCLUSIONS