Protelos Long-Term Antifracture Efficacy

Protelos Vertebral Antifracture Efficacy over 4 years in SOTI Favors Protelos  RR P< % All vertebral fractures P< % Clinical vertebral fractures

Protelos Antifracture Efficacy over 5 years in TROPOS Favors Protelos  RR P= % All non vertebral fractures P= % Major non vertebral fractures P< % All vertebral fractures

Meunier P.J et al. NEJM.2004 Reginster J.Y et al. JCEM 2005 Relative change from baseline Protelos Increase in Lumbar Spine BMD placeboProtelos 2 g/day Mean change (%) % SOTI * * * * * * Mean change (%) * * * * * * % TROPOS *P<0.001

Relative change from baseline Protelos Increase in Femoral Neck BMD placeboProtelos 2 g/day Mean change (%) % TROPOS * * * * * * Mean change (%) * * * * * * + 8.3% SOTI *P<0.001 Meunier P.J et al. NEJM.2004 Reginster J.Y et al. JCEM 2005

Protelos: BMD Changes Predict Antifracture Efficacy RR of experiencing a new clinical vertebral fracture after 3 years per 1% increase in hip BMD (after 3 years) Total hipFemoral neck RR 95% CI Bruyere et coll: ECCEO6.

Protelos: BMD Changes Predict Antifracture Efficacy RR of experiencing a new clinical vertebral fracture after 3 years in patients with or without (0%) increase in total hip or femoral neck BMD (after 3 years) Total hip BMD changes >0%Femoral neck BMD changes>0% RR 95% CI Bruyere et coll. ECCEO6.

Protelos Normalizes BMD in Osteopenic Patients 1428 subjects from SOTI and TROPOS with osteopenia at the non osteoporotic site. SR 2g/day or placebo for 4-5 years % of subjects with BMD normalized (T Score>-1) at the end of treatment RR (95% CI) Malaise O. et al. Aging in print. RR=12.38 ( ) RR=4.87 ( )

Pts % Protelos 41% 45% 37% 59% LS 72% LS/FN 56% LS/FN LS Osteoporosis + Fx Osteopenia + Fx Osteoporosis - Fx Osteopenia - Fx SOTI TROPOS Placebo Protelos Broad Range of Efficacy

Non-Vertebral Fx in Elderly Patients Patients (%) Placebo 29.0% P = RR= 0.73 [ ] N = %  RR 27% Vertebral Fracture Risk in Elderly Patients Patients (%) Placebo Protelos 35.3% 5 years P = RR= 0.69 [ ] N = %  RR 31% 35 Protelos

Treatment Effects of Protelos on Vertebral Fracture Risk Favors Protelos osteopenic without prevalent F - 72% P=0.045 Over 3 years - 38% P<0.001 Clinical VF - 45% without prevalent VF P< % with prevalent VF P<0.001 Vertebral F - 32% P=0.013  80 years Clinical VF P= %  RR After 1 year RELATIVE RISKS AND 95% CI P< % Vertebral F

Treatment Effects of Protelos on Nonvertebral Fracture Risk Major nonvertebral fractures: humerus, pelvis-sacrum, ribs-sternum, hip, clavicle, wrist. Favors Protelos Over 3 years Nonvert. fractures - 16% P=0.04 Hip fractures,  74 years - 36% P=0.046 Major nonvert. fractures - 19% P=0.031  RR - 31% Nonvert. fractures,  80 years P=

Long-Term Vertebral and Nonvertebral Fracture Risk Reductions with Protelos Favors Protelos Vertebral fractures P< %  RR Over 4 years RELATIVE RISKS AND 95% CI P< % Clinical vertebral fractures Over 5 years % P<0.001 Vertebral fractures - 15% P= % Non vertebral fractures P=0.032 Major non vertebral fractures P= % Vertebral fractures,  80 years P= % Non-vertebral fractures,  80 years

Conclusion Osteoporosis is a global burden Still many medical unmet needs Bone is a living tissue Protelos has a unique dual mode of action Protelos has the broadest range of antifracture efficacy