Preliminary Safety and Efficacy of IPI-145, a Potent Inhibitor of Phosphoinositide-3-Kinase-δ,γ in Patients with Chronic Lymphocytic Leukemia

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1 Preliminary Safety and Efficacy of IPI-145, a Potent Inhibitor of Phosphoinositide-3-Kinase-δ,γ in Patients with Chronic Session Name: 642. CLL: Therapy, excluding Transplantation: Clinical Trials of B Cell Receptor Signaling Inhibitors Session Date: Monday, December 9, 2013 Session Time: 4:30 PM - 6:00 PM Presentation Time: 5:30 PM Room: Ernest N. Morial Convention Center, Authors: Ian Flinn, MD, PhD 1 ; Manish Patel, MD 1,2 ; Brad Kahl, MD 3 ; Steven Horwitz, MD 4 ; Francine M. Foss, MD 5 ; Yasuhiro Oki, MD 6 ; Pierluigi Porcu, MD 7 ; Jennifer Sweeney 8 ; Kerstin Allen, MA 8 ; Kerrie Faia, MS 8 ; Patricia Harris, MPH 8 ; Joi Dunbar, PharmD 8 ; Howard Stern, MD, PhD 8 ; Patrick Kelly, MD 8 ; and Susan O Brien, MD 6 Affiliations: 1. Sarah Cannon Research Institute, Nashville, TN, USA; 2. Florida Cancer Specialists, Sarasota, FL, USA; 3. University of Wisconsin, Madison, WI, USA; 4. Memorial Sloan Kettering Cancer Center, New York, NY, USA; 5. Yale University Cancer Center, New Haven CT, USA; 6. MD Anderson Cancer Center, Houston, TX, USA; 7. The Ohio State University Wexner Medical Center, Columbus, OH, USA; 8. Infinity Pharmaceuticals, Inc., Cambridge, MA, USA 1

2 PI3K-δ and PI3K-γ Support the Growth and Survival of B-cell and T-cell Malignancies IPI-145 is a potent oral PI3K-δ,γ inhibitor 2

3 Phase 1 Trial of IPI-145 in Hematologic Malignancies Preliminary Outcomes in CLL Dose Escalation 8 mg BID 100 mg BID MTD = 75 mg BID R/R CLL (n=52) 61% of patients < 6 months from prior Tx 53% with 17p(del) or p53 mutation CLL cohort 1 R/R 25 mg BID n = 28 CLL cohort 2 R/R 75 mg BID n = 24 CLL cohort 3 High Risk Tx Naïve 25 mg BID n= 15 Treatment Naïve CLL (n=15) All high risk, including 7 patients with 17p(del) or p53 mutation No restriction on cytopenias in R/R CLL expansion cohorts 40% Grade 3 cytopenias at baseline 3

4 CLL Patient Disposition Median Time on Treatment, months (range) R/R CLL 25 mg BID n=28 R/R CLL 75 mg BID n=24 Tx Naïve CLL 25 mg BID n = (1 23) 5.1 (2 8) 2.7 (1 5) On Study, n (%) 1 17 (61%) 13 (54%) 14 (93%) On Treatment 14 (50%) 12 (50%) 14 (93%) Discontinued Treatment 14 (50%) 12 (50%) 1 (7%) Adverse Event 8 (29%) 5 (21%) 0 Disease Progression 4 (14%) 4 (17%) 0 Physician Decision 1 (4%) 1 (4%) 0 Death 0 2 (8%) 0 Subject Withdrawal 1 (4%) 0 1 (7%) 1 Includes patients off treatment who have not progressed 4

5 High Nodal Response Rate in CLL with IPI-145 Therapy Relapsed/Refractory CLL 98% (42/43) had a reduction in adenopathy by CT assessment 84% (36/43) with a nodal response ( 50% reduction from baseline adenopathy) Treatment Naïve / High Risk CLL With limited follow up, nodal responses in 3/6 patients, including 2 patients with p53mut 5

6 Clinical Responses in R/R CLL, Including Patients with 17p(del) or p53 mutation Population Patients (n) Best Response (n) ORR by IWCLL (CR+PR) Evaluable CR PR SD PD (%) Overall R/R CLL mg BID mg BID p(del) or p53mut

7 Adverse Events Grade 3 in CLL Patients (All Causality, 5%) IPI-145 Treatment at Recommended Phase 3 Dose (25 mg BID) 7

8 IPI-145 Efficacy and Safety Support Phase 3 Development as Monotherapy in CLL Efficacy: Evolving data suggest IPI 145 is highly active in R/R CLL ORR = 47% (1 CR) by IWCLL 84% nodal response rate Similar activity in patients with or without 17p(del) / p53mut Safety: IPI 145 safety profile supports further development Most systemic and infectious AEs were low grade Hematologic AEs were generally transient Evolving AE management paradigms allows for continued treatment Emerging data support development in other hematologic malignancies including inhl and T cell malignancies 8

9 Study IPI Acknowledgements Clinical research funded by Infinity Pharmaceuticals, Inc. We thank the investigators, study staff and sites for participating in this study. We also give a special thank you to the patients and their families for their participation and support of this research study. Sarah Cannon Research Institute, Nashville, TN: Ian Flinn, MD, Jill Harrison, Laura Dugger, Rachel Robie University of Wisconsin, Carbone Cancer Center, Madison, WI: Brad Kahl, MD, Teresa Zais Memorial Sloan Kettering, New York, New York: Steven Horwitz, MD, Megan Perez Florida Cancer Specialist, Sarasota, FL: Manish Patel, MD, Terri Peterson, Jessica Keville Yale Cancer Center, New Haven, CT: Francine Foss, MD, Diana Irizzary, Molly Daley MD Anderson Cancer Center, Houston, TX: Yasuhiro Oki, MD, Jay Knickerbocker, Carolyn Hawkins Susan O Brien, MD, Stephanie Van Derbur, Brittany Alvarez The Ohio State University, Columbus, OH: Pierluigi Porcu, MD, Michelle Messer, Stephanie Balsom 9