1. © 2014 sanofi-aventis U.S. LLC, A SANOFI COMPANY All rights reserved US.PLE.14.09.022 Brief Overview of Hematopoietic Cell Transplantation (HCT) Use

2. © 2014 sanofi-aventis U.S. LLC, A SANOFI COMPANY All rights reserved US.PLE.14.09.022 History of Early Peripheral Blood Stem Cell Transplant (PBSCT) Use 1.Goodman JW, et al. Blood. 1962;19:702-714. 2.Motabi IH, et al. Blood Rev. 2012;26(6): 267-278. 3.Kessinger A, et al. Blood. 1989;74(4):1260-1265. 4.Damon LE, et al. Expert Rev Hematol. 2009;2(6):717-733. 5.Weaver CH, et al. Blood. 1995;86:3961-3969. 2 1962 1980s 1990s and later Hematopoietic stem cells (HSC) identified in peripheral blood 1 Peripheral blood stem cells (PBSCs) facilitate recovery of hematopoietic system after myeloablation 2 PBSC transplantation used for patients unable to undergo bone marrow transplantation (BMT) 3 Collection of PBSCs using mobilization more efficient than not using mobilization 4 Validation of CD34+ cells as a surrogate for hematopoietic potential 5

3. © 2014 sanofi-aventis U.S. LLC, A SANOFI COMPANY All rights reserved US.PLE.14.09.022 Distinct Goals of Autologous HCT Therapy Goals of therapy Regenerate hematopoietic cell system after myeloablative therapy Sustained engraftment of the infused cells Benn H, et al. In: Hillyer CD, et al., eds. Blood Banking and Transfusion Medicine: Basic Principles and Practice. 2nd ed. Philadelphia, PA: Churchill Livingstone; 2006. 3

4. © 2014 sanofi-aventis U.S. LLC, A SANOFI COMPANY All rights reserved US.PLE.14.09.022 Advantages of Peripheral Blood vs Bone Marrow as Stem Cell Source Collection in outpatient setting 1 Avoidance of general anesthesia 1 Accelerated engraftment 1 Shorter duration of hospitalization 2 Improved effectiveness 1 1.Vose JM, et al. J Clin Oncol. 2002;20(9):2344-2352. 2.Schmitz N, et al. Lancet. 1996; 347:353-357. 3.Laird DJ, et al. Cell. 2008;132:612-630. 4.Benn H, et al. In: Hillyer CD, et al., eds. Blood Banking and Transfusion Medicine: Basic Principles and Practice. 2nd ed. Philadelphia, PA: Churchill Livingstone; 2006. Migrates out of the bone to the peripheral organs Physiologic circulation of stem cells Stomach Liver Stem Cell Migration 3 Returns to the bone marrow from the blood Liver Heart Given these advantages, peripheral blood has mostly replaced bone marrow as the source for autologous HCT 4 4

5. © 2014 sanofi-aventis U.S. LLC, A SANOFI COMPANY All rights reserved US.PLE.14.09.022 MOBILIZATION STRATEGIES Cytokines and Chemomobilization 5

6. © 2014 sanofi-aventis U.S. LLC, A SANOFI COMPANY All rights reserved US.PLE.14.09.022 Chemotherapy Prior to cytokines becoming widely available, only chemotherapy was in use to mobilize stem cells 1 Chemotherapy choice depends on patient treatment needs 2 Although several regimens have been used for mobilization, 2 cyclophosphamide is the most commonly used agent 3 1.Motabi IH, et al. Blood Rev. 2012;26(6): 267-278. 2.Rowley SD, et al. In: Hoffman R, et al., eds. Hematology: Basic Principles and Practice. 6th ed. Philadelphia, PA Elsevier Saunders; 2013:1472-1485. 3.Damon LE, et al. Expert Rev Hematol. 2012;2(6):717-733. Early Use of Chemotherapy to Mobilize Stem Cells 6

7. © 2014 sanofi-aventis U.S. LLC, A SANOFI COMPANY All rights reserved US.PLE.14.09.022 Mechanism of Action of Cytokine-Mediated Mobilization 1.Damon LE, et al. Expert Rev Hematol. 2009;2(6):717-733. 2.Lataillade JJ, et al. Eur Cytokine Netw. 2004;15(3):177-188. Leukocytes Stromal cells Degradation of the ECM CXCR-4 SDF-1 HSC HPC G-CSF MMP elastases cathepsin G Loss of attachment to stromal cells and the ECM EC Cytokine Mechanisms 2 Cytokines induce granulocytes, trigger the proliferation and elaboration of proteases that mediate mobilization, stimulate osteoclast activity, and down-regulate SDF 1  1 7

8. © 2014 sanofi-aventis U.S. LLC, A SANOFI COMPANY All rights reserved US.PLE.14.09.022 Mobilization of HSCs With Combined Chemotherapy and Cytokine Therapy 1.Koc ON, et al. J Clin Oncol. 2000;18:1824-1830. 2.Karanth M, et al. Bone Marrow Transplant. 2004;34:399-403. 3.Gertz MA, et al. Bone Marrow Transplant. 2009;43:619-625.. 4.Sung AD, et al. Bone Marrow Transplant. 2013;48:1444-1449. 8 a Mean CD34+ counts shown; b Median CD34+ counts shown. CLL, chronic lymphocytic leukemia; HL, Hodgkin lymphoma; NHL, non-Hodgkin lymphoma. Results without P value Not significant StudyPatient Population Mobilization Regimen CSF = Colony Stimulating Factor CD34+ Cells Collected, cells/kg Chemotherapy + Cytokines Cytokines Alone Koc et al 1,a N=29; 12 with lymphoma, 8 with MM, 9 with solid tumors Cyclophosphamide (CY) 4 g/m 2 on day 1 + CSF (36-48 h later) vs CSF (days 1-12) 3.36 × 10 6 (P=0.0075) 1.36 × 10 6 (P=0.0075) Karanth et al 2,b N=79; 22 with CLL, 35 with MM, 16 with NHL, and 6 with HL CY 2 g/m 2 on day 1 + CSF (day 5 until collection) vs CSF (days 1-5 or until collection completed) 2.2 × 10 6 2.3 × 10 6 Gertz et al 3 N=716 patients with MM CY 1.5 g/m 2 on days 1 and 2 + CSF (day 3 through collection) vs CSF (days 1 through collection; dose increases permitted) 10.3 × 10 6 (P=0.01) 9.9 × 10 6 (P=0.01) Sung et al 4,b N=226 patients 162 MM (M) 64 Lymphoma (L) Various chemotherapies – Majority CY 3 g/m 2 (97% L and 83% M) + CSF (3 days after chemotherapy for L and 4 days for M) vs. CSF (median of 10 days with CY arms and 6 days with CSF alone arms) M 13.8 × 10 6 (P<0.001) L 6.6 × 10 6 M 6.8 × 10 6 (P<0.001) L 5.5 × 10 6

9. © 2014 sanofi-aventis U.S. LLC, A SANOFI COMPANY All rights reserved US.PLE.14.09.022 *Progression: Positive immunofixation in patients who previously had a complete response after autologous SCT or 50% increase in serum or urine monoclonal protein in patients who previously had a partial response. Dingli D, et al. Clin Lymphoma Myeloma. 2006;6(5):384-388. When Used for Mobilization, Cyclophosphamide Did Not Alter Multiple Myeloma Disease Control 9 P=0.61

10. © 2014 sanofi-aventis U.S. LLC, A SANOFI COMPANY All rights reserved US.PLE.14.09.022 When Used for Mobilization, Cyclophosphamide Did Not Alter MM Disease Control Bacon et al Retrospective analysis (N=186) of patients with MM showed that, compared with cytokines alone, cytokines + high-dose cyclophosphamide was associated with –No significant differences in posttransplant efficacy outcomes –Significantly increased toxicity Bacon WA, et al. [ASH abstract 4127]. Blood. 2011;118. 10 Overall Survival Event-free Survival

11. © 2014 sanofi-aventis U.S. LLC, A SANOFI COMPANY All rights reserved US.PLE.14.09.022 Cytokines Alone Elicit Engraftment Kinetics Similar to That of Cytokines + Cyclophosphamide Desikan KR, et al. J Clin Oncol. 1998;16(4):1547-1553. Engraftment Outcome with cytokines alone compared with that achieved with cytokines + cyclophosphamide (CTX) 11 Event-free Survival

12. © 2014 sanofi-aventis U.S. LLC, A SANOFI COMPANY All rights reserved US.PLE.14.09.022 Limitations of Using Cytokines Alone Limitations: Inadequate PBSC collection in some patients Lacativa et al 1 (MM) Patient Characteristics Evaluated PBSC Failure (<4 × 10 6 cells/kg) (n=62) PBSC Success (≥4 × 10 6 cells/kg) (n=92)P Age, median years (range)60 (29-70)54 (33-67)<0.001 PBSC count before collection, median cells/kg (range) 11.5 (0-43)27 (6.9-209)<0.001 Number of sessions, n (%)* 0 1 2 3 6 (11) 10 (18) 37 (66) 3 (5) 0 46 (50) 37 (40) 9 (10) <0.001 Micallef et al 2 (NHL) Bone Marrow Infiltration(n=19)(n=33)P Any time16200.02 At diagnosis16130.002 At mobilization360.83 1.Lacativa CP, et al. Transfus Apher Sci. 2012; 47(3):331-335. 2.Micallef IN, et al. Hematol J. 2000;1(6):367-373. *Data not available in 6 patients in the failure group. 12

13. © 2014 sanofi-aventis U.S. LLC, A SANOFI COMPANY All rights reserved US.PLE.14.09.022 Limitations in Cytokine Mobilization in Patients Treated With Certain Agents Certain treatments linked to collection failure Radiation therapy 1 Radioimmunoconjugate 2 Melphalan 3 Fludarabine 4 Lenalidomide 5 1.Rowley SD, et al. In: Hoffman R, et al., eds. Hematology: Basic Principles and Practice. 6th ed. Philadelphia, PA Elsevier Saunders; 2013:1472-1485. 2.Richman CM, et al. Cancer. 1997;80(12 suppl): 2728-2732. 3.Moskowitz CH, et al. Clin Cancer Res. 1998;4(2):311-316. 4.Micallef IN, et al. Hematol J. 2000;1(6):367-373. 5.Kumar S, et al. Leukemia. 2007;21(9):2035-2042. Dex, dexamethasone; VAD, vincristine-adriamycin-dexamethasone; Thal Dex, thalidomide-dexamethasone; Len Dex, lenalidomide-dexamethasone. Effect of Lenalidomide on Mobilization 5 CD34/kg, million Total Collection Dex VAD Thal Dex Len Dex P<0.001 12.00 10.00 8.00 6.00 4.00 2.00 0.00 13

14. © 2014 sanofi-aventis U.S. LLC, A SANOFI COMPANY All rights reserved US.PLE.14.09.022 Summary 14 PBSCT has mostly replaced BMT for patients undergoing autologous HCT Mobilization strategies emerged to overcome early limitations of collecting PBSCs Using chemotherapy + cytokines for mobilization is effective but is not associated with improved outcomes versus cytokines alone