1. 1 Agenda  Overview –Burt Adelman MD  Efficacy and Pharmacodynamics –Akshay Vaishnaw MD, PhD  Safety –Gloria Vigliani MD  Alefacept Risk Benefit Profile –Mark Lebwohl MD

2. 2 Safety Overview  Size of database  Adverse Events  Serious Adverse Events  Deaths  Infection  Malignancy  Immunogenicity

3. 3 Total clinical experience (n=1357) 1 course n= 1357 2 courses n= 756 3 courses n= 199 4 courses n= 81 5 courses n= 46 Safety Database 3 placebo-controlled studies (1 course, n=876)

4. 4 Comparison of Placebo vs. Alefacept Experience 0 200 400 600 800 1000 1200 PlaceboAlefaceptTotal Alefacept 178 p-y 401 p-y 1056 p-y n= 413n= 876n= 1357 Placebo- controlled experience Person-years (p-y) exposure

5. 5 SAE55 Discontinuations12 Death0<1 Placebo(n=413) Alefacept (n= 876) Any AE 7983 Event Category % Safety Overview Placebo-Controlled Studies

6. 6 Safety Overview by Course Course 1 (n=1357) Course 2 (n=756) Course 3 (n=199) Course 4 (n=81) Course 5 (n=46) SAE54502 Discontinuations2<1110 Death<1<1<100 Any AE 8374647261 Event category (%) %%%

7. 7 Adverse Events  5% Incidence Placebo-Controlled Studies Placebo(n=413)Alefacept(n=876) EventHeadache Accidental Injury PharyngitisInfectionPruritisRhinitis Flu Syndrome Viral Infection AstheniaChillsPainDiarrheaDizzinessArthralgiaNausea 18131311810977155363171515111111966665555 %83 Percentage with an event %79

8. 8 Serious Adverse Events

9. 9 Most Frequent Serious Adverse Events* *Events occurring in >1 alefacept patient Alefacept(n=876) 2 (<1) 4 (<1) 3 (<1) 2 (<1) 42 (5%) Placebo(n=413) 6 (1) 00000 1 (<1) 00 19 (5%) Psoriasis Coronary Artery Disorder Cellulitis Myocardial Infarction Accidental Injury Carcinoma Chest Pain Diabetes Mellitus GastroenteritisPancreatitis Any SAE N (%) Placebo-Controlled First Course Experience

10. 10 Most Frequent Serious Adverse Events* Course 1 (n=1357) Course 2 (n=756) Course 3 (n=199) Course 4 (n=81) Course 5 (n=46) Any SAE N (%) 67 ( 5) 30 (4) 9 (5) 0 1 (2) Accidental Injury Psoriasis PsoriasisCellulitis Coronary Artery Disorder Skin Carcinoma Chest Pain Cholelithiasis Diabetes Mellitus Myocardial Infarct AsthmaCarcinomaGastroenteritisHerniaInfection Infection Bacterial Pancreatitis Suicide Attempt 5 ( <1) 4 ( <1) 3 ( <1) 2 ( <1) 5 ( <1) 000 1 ( <1) 0 4 ( <1) 000 1 ( <1) 0 2 ( <1) 000 1 ( <1) 0000000 000 00000000000000000000 00000000 1 (2) 00000000 *Events occurring in more than 1 patient included. Multiple Course Experience

11. 11 Deaths

12. 12 Deaths Cause of Death Age/gender Underlying factors AlefaceptReceived Suicide34M Psoriasis, family history of suicide Yes Myocardialinfarction47M CAD, HT, obesity, smoker Yes Esophagealcarcinoma53M Diaphragmatic hernia, Barrett’s esophagus Yes Myocardialinfarction52M CAD, HT No Lungcarcinoma46MSmokerYes Seizure 43M Life-long history of seizures Yes

13. 13 Infections

14. 14 Infections  5% Incidence EventPharyngitisNasopharyngitis Flu syndrome Viral infection Percentage with an infection 10% 7% 7% 5% 5% 7% 7% Placebon=413 43% Alefaceptn=876 10% 8% 8% 7% 7% 6% 6% 45% Placebo-Controlled First Course Experience

15. 15 Infections by CD4+ T Cell Counts* Alefacept Number with an infection n (%) Event n (%) PharyngitisNasopharyngitis Flu syndrome Viral infection Infection fungal Sinusitis Urinary tract infection Accidental injury BronchitisConjunctivitis Fungal dermatitis Skin infection Periodontal abscess 174 (42) 40 (10) 40 (10) 28 (7) 28 (7) 21 (5) 21 (5) 27 (7) 27 (7) 5 (1) 5 (1) 15 (4) 15 (4) 5 (1) 5 (1) 1 (<1) 1 (<1) 9 (2) 9 (2) 5 (1) 5 (1) 0 4 (<1) 4 (<1) CD4  250 (n=411) 22 (24) 8 (9) 5 (6) 4 (4) 3 (3) 2 (2) 1 (1) 1 (1) 1 (1) 1 (1) CD4<250*(n=90) 359 (46) 80 (10) 80 (10) 57 (7) 57 (7) 58 (7) 58 (7) 47 (6) 47 (6) 10 (1) 10 (1) 26 (3) 26 (3) 6 (<1) 6 (<1) 1 (<1) 1 (<1) 18 (2) 18 (2) 10 (1) 10 (1) 6 (<1) 6 (<1) 14 (2) 14 (2) CD4  250 (n=786) Placebo Placebo-Controlled First Course Experience * Only infections which occurred after the onset of CD4+ T cell count < 250 cells/uL are included

16. 16 Serious Infections Number with a serious infection N (%) Event N (%) CellulitisGastroenteritisAbscessAsthma Wound infection BronchitisPancreatitis 2 (<1) 00000 1 (<1) Placebo(n=413)Alefacept(n=876) 8 (<1) 3 (<1) 2 (<1) 1 (<1) 00 Placebo-Controlled First Course Experience

17. 17 Description DosesAge/SexDetailsPrior CD4Rechall Skin Infections: Facial cellultis1250 MObesity, DM, recurrent 343Cont. Rx otitis externa Pre-septal cellulitis1044 FSty manipulation600(placebo) Leg cellulitis152 MDM, CAD, COPD, edema, 312Withdrew erythema around plaque Finger abscess843 MOlecranon bursitis720Cont. Rx Peri-orbital infection2350 MHerpes simplex superinfection868N.A. Burn infection555 MObesity, 18x24 cm burn, DM1014Cont. Rx Toxic shock656 FCellulitis, renal and respiratory673Withdrew failure - full recovery Post-surgical Wound Infections: Post-op infection1758 MDM, rotator cuff repair616Cont. Rx Post-op infection1126 MOpen tibial fracture repair289Cont. Rx Post-op infection 1232 MPost-appendiceal rupture491Cont. Rx Serious Skin Infections - All Studies

18. 18 Infection: Conclusions  Similar incidence alefacept vs. placebo  Low CD4+ T cell counts not a risk factor  No increase by course  Uncomplicated clinical course and outcome  No opportunistic infections  No TB  No deaths due to infections

19. 19 Functional Integrity of Immune System  Preservation of naïve T cells  Partial effect against memory T cells, preservation of antibody responses  Redundancy of immune system

20. 20 Malignancy

21. 21 Number with a malignancy N (%) Event N (%) Non-melanoma skin cancer Carcinoma* Prostatic carcinoma Skin melanoma 2 (<1) 1 (<1) 0 0 Placebo(n=413)Alefacept(n=876) 10 (1) 6 (<1) 2 (<1) 1 (<1) Incidence of Malignancies *One case each of testicular and renal cell cancer Placebo-Controlled First Course Experience

22. 22 Incidence of Malignancies Number With a Malignancy n (%) Event n (%) Skin Carcinoma Carcinoma Skin Melanoma Prostatic Carcinoma Carcinoma of Lung Gastrointestinal Carcinoma* GI Neoplasia** Course 1 n=1357 Course 2 n=756 Course 3 n=199 16 ( 1) 11 (<1) 2 (<1) 1 (<1) 000 Course 4 n=81 Course 5 n=46 4 (<1) 2 (<1) 1 (<1) 000 0 4 ( 2) 2 ( 1) 000 1 (<1) 1 ( 1) 000000 1 ( 2) 000000 * One case each of adenocarcinoma of colon and esophagus ** Benign colonic polyp Multiple Course Experience

23. 23  68 yr old female  Long-standing psoriasis, previous MTX and PUVA  During third course of alefacept (total 20 injections) –Isolated 2 cm node –Follicular B cell Non-Hodgkin’s lymphoma –No other lymphoid/bone marrow involvement  Features consistent with sporadic B cell NHL and not with immunotherapy-related lesion Single case of B cell lymphoma

24. 24 Overall Malignancy Rates Incidence Rate Per 1000 Person Years (p-y) Exposure Alefacept (Overall) 22/1056 p-y Expected Rate (Psoriasis population)* 32.113 20.8 *Margolis (2001) 29 36 23

25. 25 Malignancy Conclusions  No evidence of increase in malignancy  Majority skin cancers  Observed rates for skin and total malignancies within expected rates

26. 26 Percentage Testing Positive for Anti-Alefacept Antibodies Course of Alefacept FirstSecondThirdFourthFifth Baseline During course <1 2 2 2 0 0 0 0 Number of patients dosed 13577561998146

27. 27 Safety Conclusions  Alefacept has a favorable safety profile  Similar incidence of adverse events alefacept vs. placebo  No convincing evidence of increased risk of infection or malignancy  No correlation between rates of malignancy, infections and CD4+ T cell counts  Low immunogenicity

28. 28 Plans for Extended Long-Term Safety Evaluation  Approximately 800 patients in ongoing safety-extension studies  Alefacept safety registry –powered to specifically evaluate increase in risk of adverse events of interest

29. 29 Alefacept Conclusions  Selective and novel approach targeting memory T cells  T-cell effects correlate with efficacy but not with adverse safety outcomes  Clinically meaningful benefit in the majority of patients –Significant duration of remission  Improvements in disease activity associated with QOL benefit  Well-tolerated  First systemic disease-remittive agent

30. 30 Agenda  Overview –Burt Adelman MD  Efficacy and Pharmacodynamics –Akshay Vaishnaw MD, PhD  Safety –Gloria Vigliani MD  Alefacept Risk Benefit Profile –Mark Lebwohl MD