Display 4-1: Therapies that Disqualified Patients as Responders  Phototherapy (PUVA, UVB)  Systemic retinoids  High potency topical corticosteroids  Systemic corticosteroids  Fumarates  Methotrexate, cyclosporine, azathioprine, or other systemic immunosuppressant and immunomodulatory agents  Another investigational drug or approved therapy for investigational use  Inappropriate use of moderate potency topical corticosteroids, keratolytics, coal tar, or vitamin D analogs

2 Display 4-14: Proportions of Patients Responding in Courses 1 and 2 of Study NOTE: Numbers in parentheses are percentages. P-values for comparisons with placebo. (a) From Display 4-5. Placebo IV7.5 mgPlacebo IV7.5 mgAlefacept IVAlefacept IV (Cohort 3)(Cohorts 1 and 2)(Cohort 2)(Cohort 1) Study 711 Course 1 (a)Study 711 Course 2

3 Display 4-15: Study 711 – Proportion of Patients Achieving PASI 75 by Course Placebo IV (Cohort 3) Alefacept 7.5 mg IV (Cohorts 1 and 2) Proportion responding (%) Dosing Period Proportion responding (%) Alefacept/placebo (Cohort 2) Alefacept/alefacept (Cohort 1) Dosing Period Study Week Course 1Course 2

4 Alefacept 7.5 mg IV Weekly x12Follow-Up 16 Weeks Mean Count (cells/µL) Weeks T   X174 Tetanus Toxoid CD4+ Naive CD4+ Memory    T Day 43 Day 1 Day 99Day 106Day 141 Immunizations Coincided With Maximal CD4+ Memory T-Cell Reduction

% of Patients Control Alefacept † Immunization 2nd3rd4th *2 weeks after each immunization. † P= for overall treatment difference (logistic regression model). Percentage of Patients With Anti-  X174 IgG  30% of Total Anti-  X174 Response*

6 Squamous Cell Carcinoma of Skin by Course of Alefacept * Patient also diagnosed with BCC Baseline History Patient IDCourse 1Course 2Course 3Course 4Course 5Total SCCSCCPUVAUVBMTXCyA * Total: XXXX XXXXXXXXXX XXXXXXXX XXXXXXXXXXXX X X BCC

7 Incidence of Injection Site Reactions Phase 3 IM Study No. of Patients Dosed No. with an injection site reaction No. of injections associated with an injection site reaction Placebo10 mg15 mg 168(100) 14(8) 10 (6) 4 (2) 0 173(100) 22(13) 14 (8) 6 (3) 2 (1) 0 166(100) 31(19) 20 (12) 8 (5) 0 3 (2)

8 Injection Site Reactions by Severity No. with an injection site reaction Maximum severity Mild Moderate Severe Placebo10 mg15 mg 14(100) 13 (93) 1 (7) 0 22(100) 18 (82) 4 (18) 0 31(100) 26 (84) 5 (16) 0 Phase 3 IM Study

Malignancy Rates: Invasive Squamous Cell Cancers Number of tumors per 1000 person years (p-y) exposure Placebo 0/178 p-y Alefacept (Placebo-Controlled Studies) 5/401 p-y Alefacept (Overall) 14/1056 p-y Expected Rates * ** * R. Stern (PUVA registry data, adjusted rates) **Estimated current rates, R. Stern (Personal communication)

10 Phase 3 IM Study PASI 75 at 2 Weeks After Last Dose by Quartiles of Weight Weight (kg) Proportion Responding (%) Placebo 15 mg IM Quartiles of weight are calculated using baseline weights n=46n=55 n=47n=44n=37n=45n=27n=33

11 Baseline Characteristics of Patients Who Developed SCC or BCC No. of Patients Male Age (years) Median Caucasian History of Prior SCC or BCC SCC BCC Prior Treatment of: PUVA UVB Methotrexate Cyclosporine Alefacept Treated Patients Who Developed SCC 8 (100%) 50% % 38% 25% 13% 63% 50% 75% 0% Baseline Characteristics Alefacept Treated Patients Who Developed BCC 6 (100%) 83% 62 67% 33% 17% 50% 0% Alefacept Treated Patients 1357 (100%) 69% 45 89% 3% 1% 2% 38% 45% 30% 11%

12 Mean E AUC CD4+ Memory by Weight Quartile Phase 3 IV Study Weight (kg) Mean EAUC placebo7.5 mg IV

13 Alefacept 7.5 mg IV Alefacept 15 mg IM 2 Weeks After Last Dose Overall Response Rate * P<0.001 † P=0.004 ‡ P=0.006 Efficacy Summary: IV vs IM Phase 3 Studies Alefacept 7.5 mg IV Alefacept 15 mg IM PASI 75 PGA AC/C PASI 50 Proportion Responding (%) 14% 21% 11% 14% 38% 42% * * * * † ‡ PASI 75 PGA AC/C PASI 50 Proportion Responding (%) 28% 33% 23% 24% 56% 57% * * * * * *

14 DTH Response Converting from Positive to Negative AntigenPlacebo0.025 mg/kg0.075 mg/kg0.15 mg/kg Tetanus15/32 (47)13/26 (50)18/28 (64)9/14 (64) Diphtheria4/10 (40)3/6 (50)8/11 (73) Streptococcus5/7 (71)3/3 (100)3/4 (75)5/5 (100) Tuberculin7/9 (78)7/7 (100)12/14 (86)9/11 (82) Candida3/5 (60)6/8 (75)7/8 (88)3/4 (75) Trycophyton3/3 (100)5/7 (71)4/6 (67)2/2 (100) Proteus4/11 (36)8/15 (53)6/13 (46)9/13 (69) Study Less than 30% of patients were reactive at baseline

15 DTH Response Converting from Positive to Negative AntigenPlacebo0.025 mg/kg0.075 mg/kg0.15 mg/kg Tetanus10/32 (31)9/26 (35)13/28 (46)4/14 (29) Diphtheria1/10 (10)2/6 (33)5/11 (45) Streptococcus4/7 (57)2/3 (67)2/4 (50)4/5 (80) Tuberculin5/9 (56)3/7 (43)9/14 (64)7/11 (64) Candida2/5 (40)4/8 (50)6/8 (75)2/4 (50) Trycophyton0/33/7 (43)3/6 (50)1/2 (50) Proteus2/11 (18)4/15 (27)3/13 (23)5/13 (38) Study Less than 30% of patients were reactive at baseline

16 Influence of Concomitant Medications on the Primary Endpoint PASI 75 responders n (%) irrespective of use of disqualifying meds PASI 75 responders n (%) without the use of phototherapy or other systemic therapies (pre-specified) PASI 75 responders n (%) without the use of phototherapy or other systemic therapies (Table 28) Placebo (n=186) 7.5 mg (n=367) Placebo (n=168) 15 mg (n=166) 7 (4%)55 (15%)12 (7%)37 (22%) 53 (14%)9 (5%)35 (21%) 53 (14%)8 (5%)33 (20%) P< (4%) Phase 3 Studies IV StudyIM Study

17 Range of Memory and Naïve T-Cell Counts at Baseline CD4+ Memory Cells (cells/  L) CD4+ Naïve Cells (cells/  L) CD8+ Memory Cells (cells/  L) CD8+ Naïve Cells (cells/  L) Phase 2 IV Study Phase 3 IV Study Phase 3 IM Study 81 to to to to to to to to to to to to 1237

18 Course 1 (n=1357) Course 2 (n=790*) Course 3 (n=422*) Course 4 (n=152*) Course 5 (n=116*) Any SAE** n (%) 67 ( 5) 33 (4) 15 (4) 3 (2) 2 (2) Multiple Course Experience * Number of patients in the 2nd through 5th course is estimated. **The serious adverse events represent all events reported to Biogen through May 20, 2002 Estimated Incidence of Serious Adverse Events

19 Changes in Lesional Skin: Histologic Responders vs Nonresponders Nonresponder (n=5) Responder (n=8) Number of T Cells in Epidermis Lesional NL 50 BWk2Wk6Wk13 Number of T Cells in Lesion NL 100 BWk2Wk6Wk Lesional NL = non-lesional skin at baseline. B = baseline. Epidermal Thickness (µm) NL 100 BWk2Wk6Wk13 Lesional

20 Naïve Memory CD4 CD4 Primary Response Expansion of effector CD4+ cells during active immune response T em T cm Central Memory –16% Long-term memory EffectorMemory –50% –50% *at week 13; N=21 P= Effect of Alefacept on Circulating CD4+ T-Cell Subsets*

21 Incidence of B Cell Lymphoma in Nonhuman Primates