C-SAF- 1 Raptiva ™ (efalizumab) Safety Richard Chin, MD Director of Clinical Research, Specialty Biotherapeutics Genentech, Inc.

C-SAF- 2 Outline Overview Clinical Adverse Events –During Treatment –After Treatment Laboratory Findings Extended Treatment Safety Data Summary

C-SAF- 3 Raptiva Large safety database Low overall rate of serious adverse events Well tolerated Favorable extended treatment safety profile

C-SAF- 4 Raptiva Safety Database is Extensive 2762 patients with moderate-to-severe psoriasis treated with Raptiva More than 900 patients treated with Raptiva for 6 months or longer More than 200 patients treated with Raptiva for one year or longer 1790 patient-years of experience in Raptiva treated patients Data based on BLA submitted to FDA

C-SAF- 5 Raptiva Psoriasis Studies Phase Study Number RouteStudy Design Number of Patients Enrolled III2390SCPlacebo-controlled Double-blind Randomized556 III2600SCPlacebo-controlled Double-blind Randomized686 III2058SCPlacebo-controlled Double-blind Randomized498 III2059SCPlacebo-controlled Double-blind Randomized597 III2062SCOpen-label Retreatment536 III2243SCOpen-label Long-term339 III2391SCOpen-label Follow-Up to IIHUPS252IVPlacebo-controlled Double-blind Randomized145 IHU9602IVOpen-label Single Dose31 IHUPS249IVOpen-label Multiple Dose39 IHUPS254SCOpen-label Single and Multiple Dose57 IHUPS256SC/IVOpen-label Randomized77 I2142SCOpen-label PK70

C-SAF PlaceboRaptiva 186 patient-years 1790 patient-years (n = 762*)(n = 2762) Patient-years exposure Placebo vs. Raptiva Patient-years * 715 from phase III and 47 from phase II

C-SAF- 7 Outline Overview Clinical Adverse Events –During Treatment –After Treatment Laboratory Findings Extended Treatment Safety Data Summary

C-SAF- 8 Common Adverse Events during Placebo-controlled Period Raptiva Placebo (n = 715) 1 mg/kg (n = 1213) 2 mg/kg (n = 407) Patients with at least one adverse event 73.6%82.4%87.0% Headache22.2%32.2%37.1% Chills4.5%12.7%13.0% Pain5.3%10.1%11.1% Fever3.4%6.6%11.3% Flu syndrome4.1%6.8%4.7% Nausea7.1%10.6%13.8% Myalgia4.9%8.4%7.9% Adverse events occurring in at least 5% of placebo or 1 mg/kg patients, and at least 2% more often in the 1 mg/kg group. Data from controlled studies.

C-SAF- 9 Acute Adverse Reactions % of subjects Headache, fever, chills, nausea/vomiting, or myalgia occurring within 48 hours of a Raptiva injection Weeks Placebo-controlled period from all Phase III controlled studies

C-SAF- 10 Raptiva Placebo (n = 715) 1 mg/kg (n = 1213) 2 mg/kg (n = 407) Patients with at least one serious adverse event 1.7%2.0%2.9% Cellulitis0.0%<0.1%0.5% Kidney calculus0.0%0.2% Accidental injury0.0%<0.1%0.2% Atrial fibrillation0.0%<0.1%0.2% Coronary artery disease0.0%<0.1%0.2% Gastroenteritis0.1%<0.1%0.2% Pneumonia0.0%0.2%0.0% Skin carcinoma0.1%0.2%0.0% Depression0.3%<0.1%0.0% Placebo-controlled period from all Phase III controlled studies Serious Adverse Events during Placebo-controlled Period

C-SAF- 11 Specific Adverse Events Malignancies Infections Thrombocytopenia Psoriasis and arthritis

C-SAF- 12 PlaceboRaptiva All Malignancies 1.62 (3/185 pt-yr) 1.68 (30/1782 pt-yr) NMSC 1.08 (2/186 pt-yr) 1.12 (20/1784 pt-yr) Melanoma 0.00 (0/186 pt-yr) 0.06 (1/1791 pt-yr) Solid Tumor 0.54 (1/186 pt-yr) 0.45 (8/1790 pt-yr) Lymphoma 0.00 (0/186 pt-yr) 0.06 (1/1791 pt-yr) All studies, all periods. Some patients had more than one malignancy. Malignancies Incidence per 100 patient-years

C-SAF- 13 Raptiva Placebo (n = 715) 1 mg/kg (n = 1213) 2 mg/kg (n = 407) Any diagnosis of infection 26.3%28.9%28.0% Miscellaneous infection15.4%13.7%14.5% Herpes simplex3.4%4.0%6.1% Urinary tract infection1.3%1.6%2.0% Bronchitis1.3%2.2%1.0% Viral infection1.1%2.2%0.7% Gastroenteritis3.4%2.4%1.2% Bacterial infection0.6%1.2%1.0% Otitis media1.3%1.5%1.2% Fungal dermatitis0.1%0.4%2.2% Cellulitis0.4%0.7%1.0% Fungal infection0.0%0.5%0.2% Furunculosis0.4%0.3%0.7% Placebo-controlled period from all Phase III controlled studies Infections during Placebo-controlled Period

C-SAF- 14 Serious Infections Requiring Hospitalization Incidence per 100 patient-years PlaceboRaptiva External psoriasis cohort* Incidence Rate 1.18 (2/169 pt-yrs) 1.61 (27/1681 pt-yrs) 1.8 (73/4056 pt-yrs) 95% CI0.13 – – – 2.27 * Saskatchewan Health claim database All patients, all studies

C-SAF- 15 Infections There were no deaths attributed to an infection Less than 1% discontinued treatment for a serious or non-serious infection In most cases, Raptiva was continued or was held for 1-2 doses during an infection

C-SAF- 16 Other Infections One case of legionella – recovered without sequelae Not observed: tuberculosis, pneumocystis carinii pneumonia, histoplasmosis, toxoplasmosis, Mycobacterium avium complex, etc. Rare reports of serious infections, such as vertebral osteomyelitis and severe sinusitis All studies, all periods

C-SAF- 17 Six Cases of Possible Drug-induced Immune Thrombocytopenia All platelet counts rapidly returned to baseline with Raptiva discontinuation ± corticosteroid Nadir platelet counts between 3,000 and 52,000 Causality unclear –In four of the six cases, potential other causes of thrombocytopenia included Grave’s disease (n=2), viral syndrome (n=3), and other drugs (n=1) Physicians and patients should be advised to observe for gum bleeding, petechiae, bruising

C-SAF % of placebo and 3.2% of Raptiva treated patients experienced psoriasis adverse event during the placebo-controlled period The psoriasis adverse event rate declined over time Most frequent event was mild to moderate guttate psoriasis Less than 0.5% of the patients discontinued Raptiva due to a psoriasis adverse event 5 patients (< 0.2%) experienced serious adverse event of psoriasis during treatment with Raptiva –4 events were erythrodermic psoriasis –All patients recovered without sequelae Psoriasis Adverse Events on Treatment

C-SAF- 19 Arthritis Adverse Events during Placebo-controlled Period Placebo (n = 715) 1 mg/kg (n = 1213) 2 mg/kg (n = 407) 16 (2.2%)29 (2.4%)16 (3.9%) Most events were mild to moderate in severity Most of these patients had prior history of arthritis Placebo-controlled period from all Phase III controlled studies

C-SAF- 20 Outline Overview Clinical Adverse Events –During Treatment –After Treatment Laboratory Findings Long-term Safety Data Summary

C-SAF- 21 Psoriasis during Withdrawal of Raptiva Effects of Raptiva on immune function are reversible In general, most patients return gradually to baseline/near baseline after Raptiva treatment Data from study 2059 Mean ± SE % PASI improvement Study Week Off TreatmentDuring Treatment Raptiva then Placebo Placebo WashoutTreatment

C-SAF- 22 Raptiva clinical studies imposed rigorous criteria during the follow-up period after Raptiva treatment Immediate transition to systemic therapies was prohibited Raptiva was discontinued without tapering Initially, use of other psoriasis therapies was restricted, even if the patient started experiencing return of psoriasis Restricted Use of Other Medications after Treatment with Raptiva

C-SAF % of the patients experienced psoriasis adverse events after treatment Most events were mild to moderate Half the events (6.3%) were plaque recurrence 14 patients (<1%) experienced a serious adverse event of psoriasis after Raptiva treatment (0.5% during the formal 12 week follow-up period) –Most events occurred in non-responders –Most events occurred in patients receiving more than 1 mg/kg –Types of serious adverse events: 5 erythrodermic, 5 pustular, 1 erythrodermic/pustular, 3 flare –All patients recovered Psoriasis Adverse Events after Treatment with Raptiva

C-SAF- 24 Rate No psoriasis medication15.1% (75/497) Medium potency topical steroids 5.2% (15/290) High potency topical steroids 1.1% (2/182) UVB 2.8% (2/71) Vitamin D derivative 1.0% (1/102) Systemic retinoids 0.0% (0/24) Cyclosporine 0.0% (0/54) Methotrexate 1.3% (1/77) Incidence of Psoriasis Adverse Events Patients who entered follow-up period after Raptiva treatment who had at least 2 PASI evaluations from studies 2058, 2059, 2062, and 2142 Excluding Mild Psoriasis Events (Post-hoc analysis)

C-SAF- 25 Raptiva Discontinuation: Summary There were psoriasis adverse events after Raptiva therapy, 14 of which were serious Patients should be observed carefully after treatment Transition to other therapies should be considered at discontinuation

C-SAF- 26 Arthritis Adverse Events after Treatment 4.9% of patients experienced an adverse event of arthritis after Raptiva treatment In the 1 mg/kg group, 3.7% of the patients experienced arthritis adverse events after treatment 7 patients (<1%) experienced a serious adverse event of arthritis after Raptiva treatment

C-SAF- 27 Outline Overview Clinical Adverse Events –During Treatment –After Treatment Laboratory Findings Extended Treatment Safety Data Summary

C-SAF- 28 Laboratory Findings Leukocytosis due to demargination, reversible on cessation of Raptiva Mild elevation of alkaline phosphatase (mean elevation of 6.9 U/L in the 1 mg/kg group) –No patients with Grade 2 evelvations (>2.5X normal) –Not associated with elevations in LFT’s –Not associated with clinical findings Mild elevation of C-reactive protein (mean elevation of 0.4 mg/dL in the 1 mg/kg group) –Not associated with clinical findings No sign of hepatic or renal toxicity

C-SAF- 29 Outline Overview Clinical Adverse Events –During Treatment –After Treatment Laboratory Findings Extended Treatment Safety Data Summary

C-SAF- 30 Raptiva Extended Treatment Safety Profile Week 0-12: patients from controlled studies Other weeks: patients from extended treatment studies (n = 1620)(n = 1115)(n = 318)(n = 247)(n = 228) Weeks % of patients with adverse event

C-SAF- 31 Extended Treatment Safety No new safety signals observed in the extended studies No increase in rate of individual adverse events Genentech is committed to a phase IV surveillance study to further characterize Raptiva’s long-term safety profile

C-SAF- 32 Outline Overview Clinical Adverse Events –During Treatment –After Treatment Laboratory Findings Long-term Safety Data Summary

C-SAF- 33 Summary of Clinical Safety Most common adverse events were mild flu-like symptoms Low rate of serious adverse events and malignancies, similar to placebo Low rate of serious infections, similar to expected background rate Infrequent and reversible thrombocytopenia Uncommon and manageable psoriasis adverse events No evidence of hepatic or renal toxicity Favorable extended treatment safety profile