DYNAMO: A PHASE 2 STUDY DEMONSTRATING THE CLINICAL ACTIVITY OF DUVELISIB IN PATIENTS WITH DOUBLE-REFRACTORY INDOLENT NON-HODGKIN LYMPHOMA

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1 DYNAMO: A PHASE 2 STUDY DEMONSTRATING THE CLINICAL ACTIVITY OF DUVELISIB IN PATIENTS WITH DOUBLE-REFRACTORY INDOLENT NON-HODGKIN LYMPHOMA Presented at 14-ICML, 14 June 2017, Lugano Switzerland

2 Authors Zinzani, Pier Luigi Wagner-Johnston, Nina Miller, Carole Ardeshna, Kirit Tertreault, Scott Assouline, Sarit Mayer, Jiri Michele Merli Lunin, Scott Pettitt, Andrew Nagy, Zsolt Tournilhac, Oliver Abou-Nassar, Karim Crump, Michael Jacobsen, Eric De Vos, Sven Kelly, Virginia Flinn, Ian Institutions Institute of Hematology Serágnoli, University of Bologna, Italy Siteman Cancer Center, Washington University, St Louis, USA Saint Agnes Hospital, Baltimore, USA University College London, London, UK Florida Cancer Specialists, Tallahassee, USA Jewish General Hospital, Montreal, Canada Interni hematologicka a onkologicka klinika-fn Brno, Czech Republic Ospedale Di Circolo e Fondazione Macchi U.O. Ematologia, Varese, Italy Florida Cancer Specialist, Fort Myers, USA University of Liverpool, UK Semmelweis Egyetem, I. sz. Belgyogyaszati Klinika, Budapest, Hungary CHU Estaing - Service d'hématologie, Clermont-Ferrand, France Centre intégré de santé et de services sociaux de l'outaouais, Canada Princess Margaret Cancer Center, Toronto, Canada Beth Israel Deaconess Medical Center, Boston, USA Ronald Reagan UCLA Medical Center, Los Angeles, USA Verastem Inc, Needham, USA Tennessee Oncology, Nashville, USA

3 DUVELISIB: AN ORAL DUAL INHIBITOR OF PI3K-DELTA AND PI3K-GAMMA Duvelisib synergistically targets both malignant B cells (PI3K-δ) and the supportive microenvironment (PI3K-γ) Robust clinical activity was observed in Phase 1 study in advanced B- and T-cell lymphomas (Flinn ASH 2014; O Brien ASH 2014; Horwitz ASH 2014)

4 Accrual complete Final Analysis: April 2016 Mature Follow-up: March 2017 STUDY OVERVIEW Single arm n=129 Duvelisib 25 mg BID Continuously Treatment until progression or unacceptable toxicity Response Assessments Baseline, Cycles 3, 5, 7, 10, every 4 cycles thereafter Cycle = 28 days Criteria IWG (Cheson 2007), as assessed by independent review committee (IRC) Primary Endpoint ORR = best response of CR or PR per IRC Key Secondary Endpoints Duration of response (DOR) Progression-free survival (PFS) Overall survival (OS) Safety

5 KEY ELIGIBILITY CRITERIA 3 inhl disease subtypes: follicular lymphoma (FL) (n=83) small lymphocytic lymphoma (SLL) (n=28) marginal zone lymphoma (MZL) (n=18) Patients were double-refractory to rituximab (monotherapy or in combination) and to chemotherapy or radioimmunotherapy - Refractory = no response on prior therapy, or PD within 6 months of last dose of prior therapy - Chemotherapy = alkylating agent or purine analogue No eligibility restrictions for cytopenias

6 STUDY ENROLLMENT BY REGION / COUNTRY NORTH AMERICA United States 46 Canada 9 WESTERN EUROPE Italy 21 United Kingdom 11 France 6 Belgium 2 Spain 2 EASTERN EUROPE Belarus 10 Czech Republic 9 Hungary 7 Bulgaria 5 Georgia 1

7 BASELINE CHARACTERISTICS CATEGORY OVERALL N = 129 FL N = 83 SLL N = 28 MZL N = 18 Age, median (range) 65 (30-90) 64 (30-82) 63 (48-83) 67 (41-90) Male, % ECOG - 0/1/2, % 47 / 48 / 5 51 /42/ 7 43 / 54 / 4 33 / 67 / 0 Years since diagnosis, median (range) 5 (0.3-27) 4 (0.3-27) 6 (0.9-17) 2 (0.8-10) Bulky Disease ( 5 cm), % Elevated LDH, % High FLIPI (3-5 factors), % N/A 66 N/A N/A

8 PRIOR ANTICANCER TREATMENT CATEGORY OVERALL N = 129 FL N = 83 SLL N = 28 MZL N = 18 Number of Prior Anticancer Regimens Median Min, Max 1, 18 1, 10 1, 18 1, 8 2, % > 2, % Time since completion of last therapy (months) Median Min, Max 0, 121 0, 121 1, 74 1, 58

9 REFRACTORY TO SELECT PRIOR ANTICANCER THERAPY CATEGORY Overall N=129 % FL N=83 % SLL N=28 % MZL N=18 % Refractory to last therapy Refractory to at least 2 therapies Rituximab Alkylating Agent and/or Purine Analogue Rituximab + Alkylating Agent Bendamustine + rituximab R-CHOP R-CVP

10 OVERALL RESPONSE RATE OVERALL N = 129 FL N = 83 SLL N = 28 MZL N = 18 ORR per IRC 47% 43% 68% 33% P-value p = % CI (38-56) Complete Response 1% 1% 0 0 Partial Response 47% 42% 68% 33% ORR per Investigator 60% 53% 86% 50% Complete Response 3% 2% 4% 6% Partial Response 57% 51% 82% 44% Rapid time to response: median 2 months (range: ) Primary endpoint met at final analysis Median time on duvelisib: 7 months (range: )

11 PERCENT CHANGE IN NODAL TARGET LESIONS 88% of patients had reduction in target lymph nodes (IRC data)

12 DURATION OF RESPONSE Population Median (months) 95% CI All inhl , 10.3 FL , 12.6 SLL , 10.5 MZL , NE

13 PROGRESSION-FREE SURVIVAL Population Median (months) 95% CI All inhl , 11.8 FL , 11.0 SLL , 12.1 MZL , NE

14 OVERALL SURVIVAL Population Median (months) 95% CI All inhl , NE FL , NE SLL , NE MZL NE 12.4, NE

15 MOST COMMON AEs (N=129) ( 15% ANY GR, OR >5% GR 3-4) Preferred Term All Grades Gr 3 Gr 4 % % % Hematologic Neutropenia Anemia Thrombocytopenia Nonhematologic Diarrhea Nausea Cough Fatigue Pyrexia Rash Vomiting Peripheral edema Headache Decreased appetite Febrile neutropenia Investigations ALT increased Lipase increased 9 3 4

16 ADVERSE EVENTS OF INTEREST Few discontinuations due to severe AEs of interest Serious opportunistic infections < 4%: PCP (unconfirmed) (n=1); CMV (n=2); fungal pneumonia (n=2) Deaths attributed to treatment (n=6)* *colitis (n=1); toxic epidermal necrolysis/sepsis syndrome (n=1); drug reaction/eosinophilia/systemic symptoms (n=1); pneumonitis/pneumonia (n=1); viral infection (n=1); septic shock (n=1)

17 DYNAMO STUDY CONCLUSIONS Duvelisib monotherapy is clinically active in double-refractory inhl ORR of 47% per IRC; ORR of 60% per Investigator 88% of patients had tumor reduction Responses were durable (median 10 months) Duvelisib has a manageable safety profile In long-term follow-up (median 18 months), duvelisib remains well tolerated Duvelisib showed favorable risk-benefit in double-refractory inhl, and may represent an important treatment option for these patients

18 THANK YOU We would like to acknowledge the participating institutions, their study investigators and clinical staff, for the successful conduct of the study. Most importantly, we sincerely thank our patients and their families for their participation in this clinical study.