1. Active Immunotherapy with Mitumprotimut-T Following Rituximab Induction in Patients with Follicular B-cell Lymphoma: Progression-Free Survival at 4-year Follow-Up Omer Koc, MD; Charles Redfern, MD; Peter Wiernik, MD; Fred Rosenfelt, MD; Jane Winter, MD; Troy Guthrie, MD; Lawrence Kaplan, MD; Peter Holman, MD; John Densmore, MD; John Hainsworth, MD; Thomas Lin, MD, PhD; Rene Castillo, MD; Nalini Janakiraman, MD and John Bender, PharmD Presented December 9, 2007, at the 49th ASH Annual Meeting in Atlanta, Georgia

2. Active Immunotherapy with Mitumprotimut-T Following Rituximab Induction in Patients with Follicular B-cell Lymphoma: Progression-Free Survival at 4-year Follow-Up Mitumprotimut-T is a patient-specific and B-cell tumor-specific idiotype (Id) protein chemically conjugated to keyhole limpet hemocyanin (KLH), a potent non-specific immunogenic protein Mitumprotimut-T induces a cellular and humoral immune response to the Id protein expressed by the patient’s own tumor, leading to active immunization against the tumor while sparing normal B-cells Background Omer K et al. Abstract #2567. Presented December 9, 2007, at the 49th ASH Annual Meeting in Atlanta, Georgia.

3. Active Immunotherapy with Mitumprotimut-T Following Rituximab Induction in Patients with Follicular B-cell Lymphoma: Progression-Free Survival at 4-year Follow-Up Mitumprotimut-T is co-administered with GM-CSF to further enhance immune anti-Id immune responses The Id protein is produced by proprietary recombinant technology; ~8 weeks from biopsy to final product Background Omer K et al. Abstract #2567. Presented December 9, 2007, at the 49th ASH Annual Meeting in Atlanta, Georgia.

4. Active Immunotherapy with Mitumprotimut-T Following Rituximab Induction in Patients with Follicular B-cell Lymphoma: Progression-Free Survival at 4-year Follow-Up To compare the progression-free survival (PFS) in patients treated with rituximab followed by mitumprotimut-T and GM-CSF to historical data with rituximab alone To evaluate the safety of this combination regimen Objectives Omer K et al. Abstract #2567. Presented December 9, 2007, at the 49th ASH Annual Meeting in Atlanta, Georgia.

5. Active Immunotherapy with Mitumprotimut-T Following Rituximab Induction in Patients with Follicular B-cell Lymphoma: Progression-Free Survival at 4-year Follow-Up Key Inclusion Criteria – Histologically confirmed Grade 1 or 2 follicular B-cell lymphoma (WHO classification) – Treatment-naïve, relapsed/refractory to chemotherapy, or relapsed following prior ≥ 6-month response to rituximab – ≥8 weeks between completion of any prior lymphoma therapy and start of rituximab on study – Measurable disease (≥2 cm) following node biopsy – Performance status (ECOG) of 0, 1 or 2 Methods Omer K et al. Abstract #2567. Presented December 9, 2007, at the 49th ASH Annual Meeting in Atlanta, Georgia.

6. Active Immunotherapy with Mitumprotimut-T Following Rituximab Induction in Patients with Follicular B-cell Lymphoma: Progression-Free Survival at 4-year Follow-Up Key Exclusion Criteria – >3 prior chemotherapy or anti-CD20 regimens – Prior fludarabine – Concurrent immunosuppressive therapy (e.g., high-dose steroids) Methods Omer K et al. Abstract #2567. Presented December 9, 2007, at the 49th ASH Annual Meeting in Atlanta, Georgia.

7. Active Immunotherapy with Mitumprotimut-T Following Rituximab Induction in Patients with Follicular B-cell Lymphoma: Progression-Free Survival at 4-year Follow-Up Treatment Regimen Rituximab: 375 mg/m2 weekly infusion x 4 weeks. Subjects with stable disease (SD) or an objective response (CR or PR) to rituximab were eligible for mitumprotimut-T Mitumprotimut-T: 1 mg sc on Day 1 of each course. Courses administered monthly x6, bimonthly x6, and then every 3 months until disease progression or significant toxicity GM-CSF: 250 mcg/day sc on Days 1-4 of each course; same injection site as mitumprotimut-T CT scans: Obtained every 3 months; read by an independent radiologist blinded to clinical data Methods Omer K et al. Abstract #2567. Presented December 9, 2007, at the 49th ASH Annual Meeting in Atlanta, Georgia.

8. Study Schema and Treatment Regimen 0 3 6 912 15 18 21 24 Months CT Scans Mitumprotimut-T + GM-CSF Rituximab Mitumprotimut-T Production Biopsy Cytoreduction Induction Maintenance Omer K et al. Abstract #2567. Presented December 9, 2007, at the 49th ASH Annual Meeting in Atlanta, Georgia.

9. Patient Characteristics at Study Entry Omer K et al. Abstract #2567. Presented December 9, 2007, at the 49th ASH Annual Meeting in Atlanta, Georgia. CharacteristicN = 89 Age Median (range)53 (30 – 85) years Gender, n (%) Male 47 (53%) Female42 (47%) Follicular Lymphoma WHO Grade, n (%) Grade 147 (53%) Grade 238 (43%) Grade 32 (2%) Not reported2 (2%)

10. Patient Characteristics at Study Entry Omer K et al. Abstract #2567. Presented December 9, 2007, at the 49th ASH Annual Meeting in Atlanta, Georgia. CharacteristicN = 89 Treatment History, n (%) Treatment-naïve (T-N)35 (39%) Relapsed/Refractory (R/R)54 (61%) No. of Prior Systemic Therapies (n = 54 R/R) Median (range)1.5 (1 – 4) FLIPI Risk Group, n (%) Low16 (18%) Intermediate26 (29%) High20 (23%) Not evaluable27 (30%)

11. Active Immunotherapy with Mitumprotimut-T Following Rituximab Induction in Patients with Follicular B-cell Lymphoma: Progression-Free Survival at 4-year Follow-Up Adverse Events – Adverse events were collected for 103 patients enrolled in the study, including 9 who received rituximab alone and 94 who received rituximab followed by at least one dose of mitumprotimut-T + GM-CSF – Most adverse events were of severity Grade 1 or 2 (NCI-CTC version 2) – The most common adverse event was injection site reaction, which was reported in 82 patients (79.6%), with 81 (78.6%) at Grade 1-2 and 1 (1%) at Grade 3 severity – No Grade 4 severity was reported for any of these adverse events Results Omer K et al. Abstract #2567. Presented December 9, 2007, at the 49th ASH Annual Meeting in Atlanta, Georgia.

12. Adverse Events Omer K et al. Abstract #2567. Presented December 9, 2007, at the 49th ASH Annual Meeting in Atlanta, Georgia. Percent of PatientsAdverse Event >75%Injection site reaction >25% to 50%Fatigue, myalgia, headache, arthralgia, chills >10% to 25%Nausea, pyrexia, insomnia, back pain, diarrhea, abdominal pain, flu-like symptoms, peripheral edema, pain, pruritus, upper respiratory track infection, cough, night sweats, dyspepsia, pain in extremity, dyspnea, pharyngolaryngeal pain, rash, vomiting

13. Progression Free Survival (PFS) T-N = treatment-naïve, R/R = relapse-refractory. Omer K et al. Abstract #2567. Presented December 9, 2007, at the 49th ASH Annual Meeting in Atlanta, Georgia. By Treatment History GroupN12 mos24 mos36 mos48 mos All Subjects8960%37%30%26% R/R Subjects5456%30%20%17% T-N Subjects3567%48%44%40% By Response To Rituximab Cytoreduction GroupN12 mos24 mos36 mos48 mos All Rituximab Responders4369%50%43%40% R/R Rituximab Responders1963%41%33% T-N Rituximab Responders2475%57%51%45%

14. Progression-Free Survival in Treatment-Naïve Patients Omer K et al. Abstract #2567. Presented December 9, 2007, at the 49th ASH Annual Meeting in Atlanta, Georgia. 0 3 6 954 57 60 63 42 45 48 51 30 33 36 3918 21 24 2712 15 0 10 20 30 40 50 60 70 80 90 100 Time From First Dose of Rituximab (months) Percent Surviving Progression-Free T-N Rituximab Responders (N=24) T-N (N=35) Censored, Ongoing Censored, Permanent

15. Progression-Free Survival in Relapsed/Refractory Patients Omer K et al. Abstract #2567. Presented December 9, 2007, at the 49th ASH Annual Meeting in Atlanta, Georgia. 0 3 6 954 57 60 63 42 45 48 51 30 33 36 3918 21 24 2712 15 0 10 20 30 40 50 60 70 80 90 100 R/R Rituximab Responders (N=19) R/R (N=54) Censored, Ongoing Censored, Permanent Time From First Dose of Rituximab (months) Percent Surviving Progression-Free

16. Disease Response Assessment 27 patients (30%) had a response improvement during treatment with mitumprotimut-T + GM-CSF: 11 SD converted to PR, 1 SD converted to CR, 15 PR converted to CR. Omer K et al. Abstract #2567. Presented December 9, 2007, at the 49th ASH Annual Meeting in Atlanta, Georgia. ~3 Months After Start Rituximab (Before Start of Mitumprotimut-T) Any Time After Start of Mitumprotimut-T + GM-CSF Overall N = 89 T-N N = 35 R/R N = 54 Overall N = 89 T-N N = 35 R/R N = 54 Complete Response 2 (2.2%) 02 (3.7%) 18 (20.2%) 9 (25.7%) 9 (16.7%) Partial Response 41 (46.1%) 24 (68.6%) 17 (31.5%) 37 (41.6%) 18 (51.4%) 19 (35.2%) Objective Response 42 (48.3%) 24 (68.6%) 19 (35.2%) 55 (61.8%) 27 (77.1%) 28 (51.9%) Stable Disease 43 (48.3%) 11 (31.4%) 32 (59.2%) 31 (34.8%) 8 (22.9%) 23 (42.6%) Progressive Disease ‡ 3 (3.4%) 03 (5.6%) 3 (3.4%) 03 (5.6%)

17. Results of Study FavId-04 and Studies of 4-Weekly Doses of Rituximab in Treatment-Naïve Follicular Lymphoma Patients * From progression-free survival KM curve for all patients. ‡ From duration of response KM curve for rituximab responders (CR or PR) only. N/R = not reported in manuscript. Omer K et al. Abstract #2567. Presented December 9, 2007, at the 49th ASH Annual Meeting in Atlanta, Georgia. Percent of Patients Author/ReferenceNo. of Pts.Progression-Free*Continued Response ‡ Study FavId-043544% at 3 years51% at 3 years Witzig et al, J Clin Oncol 2004;23:1103 3621% at 3 yearsN/R Colombat et al, Blood 2006;108:#486 49N/R24% at 5 years Ghielmini et al, Blood 2004;103:4416 26N/R20% at 3 years

18. Active Immunotherapy with Mitumprotimut-T Following Rituximab Induction in Patients with Follicular B-cell Lymphoma: Progression-Free Survival at 4-year Follow-Up The progression-free survival (PFS) KM curves appear to be biphasic, with a substantial proportion of patients remaining free of progression beyond 4 years: – 26% of all patients – 40% of treatment-naïve patients – 45% of treatment-naïve patients who responded to rituximab Summary Omer K et al. Abstract #2567. Presented December 9, 2007, at the 49th ASH Annual Meeting in Atlanta, Georgia.

19. Active Immunotherapy with Mitumprotimut-T Following Rituximab Induction in Patients with Follicular B-cell Lymphoma: Progression-Free Survival at 4-year Follow-Up In treatment-naïve patients, the overall 3-year PFS rate with rituximab followed by mitumprotimut-T + GM-CSF is 44% vs. 21% with rituximab alone (Witzig et al), and the 3-year continued response rate is 51% with rituximab followed by mitumprotimut-T + GM-CSF vs. 20% with rituximab alone (Ghielmini et al) Patients who achieved an objective response (CR or PR) following rituximab and then received mitumprotimut-T + GM-CSF had longer PFS than patients with stable disease after rituximab Summary Omer K et al. Abstract #2567. Presented December 9, 2007, at the 49th ASH Annual Meeting in Atlanta, Georgia.

20. Active Immunotherapy with Mitumprotimut-T Following Rituximab Induction in Patients with Follicular B-cell Lymphoma: Progression-Free Survival at 4-year Follow-Up The progression-free survival and duration of response in this study suggest a better clinical outcome when mitumprotimut-T + GM-CSF is given following cytoreductive therapy with rituximab than would be expected with single-agent rituximab treatment Conclusions Omer K et al. Abstract #2567. Presented December 9, 2007, at the 49th ASH Annual Meeting in Atlanta, Georgia.

21. Active Immunotherapy with Mitumprotimut-T Following Rituximab Induction in Patients with Follicular B-cell Lymphoma: Progression-Free Survival at 4-year Follow-Up This hypothesis is being tested in an ongoing Phase 3 registration trial in which subjects with follicular lymphoma randomized to receive mitumprotimut-T or placebo, both with GM-CSF, following cytoreduction with rituximab achieved a best objective response rate of 70% (CR = 47%, PR = 23%) in a blinded interim analysis (Freedman et al, Blood 2006; 108: #2756) Analysis of time to progression, the study primary efficacy endpoint, is expected in July 2008 Conclusions Omer K et al. Abstract #2567. Presented December 9, 2007, at the 49th ASH Annual Meeting in Atlanta, Georgia.