International Conference on Malignant Lymphoma (ICML) June 14-17, 2017

International Conference on Malignant Lymphoma (ICML) June 14-17, 2017 INTERIM REPORT FROM A PHASE 2 MULTICENTER STUDY OF TAZEMETOSTAT, AN EZH2 INHIBITOR: CLINICAL ACTIVITY AND FAVORABLE SAFETY IN PATIENTS WITH RELAPSED OR REFRACTORY B-CELL NON-HODGKIN LYMPHOMA Franck Morschhauser, Gilles Salles, Pamela McKay, Hervé Tilly, Anna Schmitt, John Gerecitano, Peter Johnson, Steven Le Gouill, Michael J. Dickinson, Christophe Fruchart, Thierry Lamy, Aristeidis Chaidos, Wojciech Jurczak, Stephen Opat, John Radford, Pier Luigi Zinzani, Sarit Assouline, Guillaume Cartron, Alicia Clawson, Natasha Picazio, Scott Ribich, Stephen J. Blakemore, John Larus, Harry Miao, Mark Woodruff, Peter T. Ho, Vincent Ribrag 1

TAZEMETOSTAT FOR THE TREATMENT OF B-CELL NHL EZH2 is an epigenetic regulator of gene expression and plays a critical role in multiple forms of cancer PRC2 Activating mutations of EZH2 can act as an oncogenic driver for cancers, especially in FL and GCB-DLBCL, present in ~20% of patients EZH2 Y646F/N/H/S/C A682G A692V Tazemetostat First-in-class, potent and selective oral inhibitor of mutated and wild-type EZH2 Preclinical activity in DLBCL cells lines, with greater activity in EZH2 mutant models Monotherapy activity and favorable safety in phase 1 studies in patients with relapsed or refractory (R/R) NHL, as well as certain genetically defined solid tumors Tazemetostat K27me3 K27me3 K27me3 K27me3 Compacted Chromatin Transcriptional Repression 2

TAZEMETOSTAT PHASE 2 NHL STUDY DESIGN Global, multi-center, open-label study in 6 cohorts of patients with R/R DLBCL or FL Patients prospectively stratified by EZH2 mutational status and cell of origin 2 prior therapies Primary endpoint: overall response rate 1 (ORR) Secondary efficacy endpoints: progression-free survival (PFS) and duration of response Study initiated with 5 monotherapy cohorts (n=270) 3 cohorts of DLBCL (n=60 each) and 2 cohorts of FL (n=45 each) Cohort of tazemetostat + prednisolone (n=70) in DLBCL added in 2017 PRE-SCREENING Archival Tissue Central Lab COO, EZH2 COHORT ALLOCATION DLBCL, GCB EZH2 Mt (N=60) DLBCL, GCB EZH2 WT (N=60) DLBCL, NON-GCB (N=60) FL, EZH2 Mt (N=45) FL, EZH2 WT (N=45) ELIGIBILTY, ENROLLMENT Tazemetostat, 800 mg BID until PD or withdrawal ORR, PFS, DOR, safety, PK EOT FOLLOW-UP OS 1 Objective response assessed by IWG-NHL criteria (Cheson 2007) Restaging every 8 weeks for 6 cycles, then every 12 weeks thereafter 3

PROTOCOL SPECIFIED MOLECULAR CHARACTERIZATION OF B-CELL NHL PATIENTS Prospective testing: required for cohort allocation FL & DLBCL cobas EZH2 Mutation Test (Roche Molecular Systems, in development) Allele specific PCR test for EZH2 hot spot mutations DLBCL only Hans IHC for determination of cell of origin (COO) Retrospective testing: NGS on archival and circulating tumor DNA collected at screening for common NHL mutations in a panel of 62 genes Lymph2Cx nanostring assay for more accurate COO determination Published discordance rate of ~20% between nanostring vs. Hans 4

PHASE 2 NHL STUDY PROGRESS Data cut-off: June 1, 2017 218 patients enrolled into monotherapy cohorts 81% of total of 270 Closed to accrual: FL wild-type EZH2 54 pts, 54 evaluable for efficacy DLBCL wild-type EZH2 (GCB EZH2 WT + non-gcb) 120 pts, 119 evaluable for efficacy Open to accrual: FL mutated EZH2 19 pts, 13 evaluable for efficacy DLBCL mutated EZH2 22 pts, 17 evaluable for efficacy Evaluable population Safety: 210 pts Efficacy: 203 pts 5

PHASE 2 NHL DEMOGRAPHICS & DISEASE CHARACTERISTICS Characteristic Follicular Lymphoma DLBCL EZH2 Status Mutant Wild-type Mutant Wild-type n 13 54 17 120 Age, median years 62 61 61 69 Males 46% 63% 53% 58% ECOG PS, median (range) 0 (0-2) 0 (0-2) 1 (0-2) 1 (0-2) Prior lines of therapy, n (%) 1 1 ( 8%) 0 0 3 ( 3%) 2 2 (15%) 11 (20%) 4 (24%) 40 (33%) 3 3 (23%) 9 (17%) 7 (41%) 28 (23%) 4 1 ( 8%) 14 (26%) 3 (18%) 18 (15%) 5 6 (46%) 20 (37%) 3 (18%) 31 (26%) median 4 4 3 3 Refractory to last regimen, n (%) 7 (54%) 26 (48%) 14 (82%) 75 (63%) Prior HSCT 23% 41% 41% 24% Median time from initial diagnosis years 7.4 4.9 1.0 2.0 Median time from last prior therapy weeks 13.0 41.3 8.6 11.6 Data as of 6/1/2017 Refractory to last regimen defined as SD or PD as best response to most recent prior therapy 6

PHASE 2 NHL DEMOGRAPHICS & DISEASE CHARACTERISTICS Characteristic Follicular Lymphoma DLBCL EZH2 Status Mutant Wild-type Mutant Wild-type n 13 54 17 120 Age, median years 62 61 61 69 Males 46% 63% 53% 58% ECOG PS, median (range) 0 (0-2) 0 (0-2) 1 (0-2) 1 (0-2) Prior lines of therapy, n (%) 1 1 ( 8%) 0 0 3 ( 3%) 2 2 (15%) 11 (20%) 4 (24%) 40 (33%) 3 3 (23%) 9 (17%) 7 (41%) 28 (23%) 4 1 ( 8%) 14 (26%) 3 (18%) 18 (15%) 5 6 (46%) 20 (37%) 3 (18%) 31 (26%) median 4 4 3 3 Refractory to last regimen, n (%) 7 (54%) 26 (48%) 14 (82%) 75 (63%) Prior HSCT 23% 41% 41% 24% Median time from initial diagnosis years 7.4 4.9 1.0 2.0 Median time from last prior therapy weeks 13.0 41.3 8.6 11.6 Data as of 6/1/2017 Refractory to last regimen defined as SD or PD as best response to most recent prior therapy 7

PHASE 2 NHL DEMOGRAPHICS & DISEASE CHARACTERISTICS Characteristic Follicular Lymphoma DLBCL EZH2 Status Mutant Wild-type Mutant Wild-type n 13 54 17 120 Age, median years 62 61 61 69 Males 46% 63% 53% 58% ECOG PS, median (range) 0 (0-2) 0 (0-2) 1 (0-2) 1 (0-2) Prior lines of therapy, n (%) 1 1 ( 8%) 0 0 3 ( 3%) 2 2 (15%) 11 (20%) 4 (24%) 40 (33%) 3 3 (23%) 9 (17%) 7 (41%) 28 (23%) 4 1 ( 8%) 14 (26%) 3 (18%) 18 (15%) 5 6 (46%) 20 (37%) 3 (18%) 31 (26%) median 4 4 3 3 Refractory to last regimen, n (%) 7 (54%) 26 (48%) 14 (82%) 75 (63%) Prior HSCT 23% 41% 41% 24% Median time from initial diagnosis years 7.4 4.9 1.0 2.0 Median time from last prior therapy weeks 13.0 41.3 8.6 11.6 Data as of 6/1/2017 Refractory to last regimen defined as SD or PD as best response to most recent prior therapy 8

TAZEMETOSTAT DEMONSTRATED FAVORABLE SAFETY PROFILE Treatment-Emergent Adverse Event All TEAEs Patients (n=210) with: Treatment-Related TEAEs All Grades Grade 3 All Grades Grade 3 Nausea 42 (20%) 1 (<1%) 29 (14%) 0 Thrombocytopenia 39 (19%) 19 ( 9%) 28 (13%) 12 ( 6%) Anaemia 33 (16%) 16 ( 8%) 21 (10%) 9 ( 4%) Cough 30 (14%) 1 (<1%) 4 ( 2%) 1 (<1%) Fatigue 26 (12%) 5 ( 2%) 15 ( 7%) 2 ( 1%) Diarrhoea 24 (11%) 1 (<1%) 17 ( 8%) 1 (<1%) Asthenia 22 (10%) 3 ( 1%) 16 ( 8%) 1 (<1%) Neutropenia 21 (10%) 15 ( 7%) 19 ( 9%) 13 ( 6%) Pyrexia 21 (10%) 1 (<1%) 2 ( 1%) 0 Vomiting 21 (10%) 2 ( 1%) 7 ( 3%) 1 (<1%) Bronchitis 14 ( 7%) 0 2 ( 1%) 0 Constipation 13 ( 6%) 1 (<1%) 4 ( 2%) 1 (<1%) Decreased appetite 13 ( 6%) 0 6 ( 3%) 0 Upper respiratory tract infection 13 ( 6%) 0 1 (<1%) 0 Abdominal pain 12 ( 6%) 3 ( 1%) 4 ( 2%) 0 Headache 12 ( 6%) 0 4 ( 2%) 0 Urinary tract infection 12 ( 6%) 0 4 ( 2%) 0 Back pain 11 ( 5%) 2 ( 1%) 1 (<1%) 0 Oedema peripheral 11 ( 5%) 2 ( 1%) 1 (<1%) 0 Dysgeusia 10 ( 5%) 0 7 ( 3%) 0 Rhinitis 10 ( 5%) 0 1 (<1%) 0 9 1 One (1) TEAEs of Febrile Neutropenia Data as of 6/1/2017 Adverse events reported in 5% of patients

ADVERSE EVENTS LED TO LOW RATE OF DOSE REDUCTIONS AND DISCONTINUATIONS Patients (n=210) Treatment-Emergent Adverse Events (TEAEs) * Treatment-Related TEAEs Adverse Event (any) 190 (90%) 123 (59%) Grade 3 91 (43%) 38 (18%) Serious AE 81 (39%) 20 (10%) AE Leading to Dose Interruption 50 (24%) 31 (15%) AE Leading to Dose Reduction 8 ( 4%) 7 ( 3%) AE Leading to Drug Discontinuation or Study Withdrawal 26 (12%) 5 ( 2%) Data as of 6/1/2017 * TEAEs are adverse events that first appear during treatment, which were absent before or which worsen relative to the pre-treatment 10

TAZEMETOSTAT DEMONSTRATED HIGHER RESPONSE RATES IN EZH2 MUTATED NHL Best Response FL EZH2 MT (n=13) FL EZH2 WT (n=54) DLBCL EZH2 MT (n=17) DLBCL EZH2 WT (n=119) Objective Response Rate (CR + PR) 12 (92%) 14 (26%) 5 (29%) 18 (15%) Complete Response (CR) 1 (8%) 3 (6%) 0 10 (8%) Partial Response (PR) 11 (85%) 11 (20%) 5 (29%) 8 (7%) Stable Disease 1 (8%) 23 (43%) 6 (35%) 22 (18%) SD study drug ongoing 1 (8%) 12 (22%) 1 (6%) 4 (3%) Progressive Disease 0 13 (24%) 6 (35%) 60 (50%) No Data, Unknown (UNK) 0 4 (7%) 0 19 (16%) Time to first Response (wks) median (range) 11.9 (6.9 35.9) 15.2 (8.1-32.1) 8.3 (4.6 48.1) 8.5 (5.3 24.7) Data as of 06/1/2017 Ongoing patients with Best Response of 'No Data, Unknown' are not included in this table 11

TUMOR REDUCTION IN FOLLICULAR LYMPHOMA 75% of patients experienced reduction of tumor burden Data as of 6/1/2017 12

DURATION OF TUMOR RESPONSE IN FOLLICULAR LYMPHOMA 48% of patients remain on study 0 5 10 15 Months Since Treatment Initiation Data as of 6/1/2017 13

TUMOR RESPONSE IN FL WITH MUTATED EZH2 cobas Test Y646F;; NGS Y646F;; ctdna Y646F 68 y.o female Baseline Week 24 Chlorambucil Prednisone R-CHOP PI3K/mTOR inhibitor Tazemetostat: week 36+ 1998 1999 2007 2012 2014 CR CR SD 2016 2017 PR at week16 14

DURATION OF TUMOR RESPONSE IN DLBCL Data as of 6/1/2017 12% of patients remain on study 0 5 10 15 20 Months Since Treatment Initiation 15

TUMOR RESPONSE IN DLBCL WITH MUTATED EZH2 cobas Test Y646X;; NGS Y646H;; ctdna Y646H 61 y.o. male 1 0 0 0 0 L e s i o n s i z e, S P D 8 0 0 0 6 0 0 0 4 0 0 0 2 0 0 0 0 0 2 0 4 0 6 0 Baseline Week 24 T i m e p o s t t r e a t m e n t, w k R-CHOP Carmustine Etoposide Cytarabine Melphalan Rituximab Epratuzumab ha20 Rituximab Lenalidomide Obinutuzumab Bendamustine Tazemetostat: week 60+ 1999 2003 2005 2007 2012 2014 CR PR PR PR PD SD 2016 2017 PR at week 48 16

RESPONSE AFTER INITIAL DISEASE PROGRESSION IN DLBCL NON-GCB (PMBCL) 36 y.o. male 1 5 0 0 0 L e s io n s iz e, S P D 1 0 0 0 0 5 0 0 0 0 0 8 1 6 2 4 T im e p o s t tr e a tm e n t, w k Screening Week 8 Week 16 17

NGS analysis performed on archive tumor and circulating tumor DNA (ctdna) for a subset (n = 92) of patients Custom 62 gene panel includes common NHL somatic mutations Responder (CR+PR) vs. Non-Responder analyses Details presented in Poster #154 (Blakemore et al.) Results: MOLECULAR PROFILING IDENTIFIES POTENTIAL TAZEMETOSTAT RESPONSE PREDICTORS Positive and negative predictors for tazemetostat response (PR/CR) identified Positive predictors = EZH2 & MYD88 activating mutations Negative predictors = MYC, TP53 and HIST1H1E EZH2 and MYD88 mutually exclusive in this cohort i.e. potential for independent mechanism of sensitivity to tazemetostat in these patients Patients, % 100 80 60 40 20 0 7 3 EZH2 MT 18 63 EZH2 WT Patients, % 100 80 60 40 20 0 4 3 MYD88 MT 21 64 MYD88 WT Non-Responder Responder Non-Responder Responder Detection of EZH2 mutations in ctdna indicates potential for future potential use of plasma for patient identification Data as of 6/1/2017 18

SUMMARY Tazemetostat shows efficacy in heavily pretreated relapsed/refractory FL and DLBCL Follicular Lymphoma 92% ORR in patients with mutated EZH2 26% ORR in patients with wild-type EZH2 with 22% of patients on-study in SD 48% overall with treatment ongoing DLBCL 29% ORR in patients with mutated EZH2 15% ORR with 8% CRs in WT patients Durable responses in both WT and mutants Late responses and conversion to CR in both subtypes Molecular profiling may help predict response Tazemetostat is safe Low incidence of treatment-related grade 3, mainly thrombocytopenia (6%) and neutropenia (6%) Enrollment of EZH2 mutated DLBCL and FL continues 19

ACKNOWLEDGEMENTS We wish to thank all of the physicians, nurses, study staff, scientists, and most of all, the patients and families who contributed to this study 20