1. Limbs International Medical Buflomedil Trial Presented at American College of Cardiology Scientific Sessions 2005 Presented by Dr. Alain Leizorovicz LIMB

2. www. Clinical trial results.org Endpoints (median follow-up 2.75 years):  Primary: Composite of clinical deterioration of symptoms, fatal or non-fatal cardiovascular events, lower limb arterial surgery or angioplasty and amputation  Secondary: individual components of primary composite Endpoints (median follow-up 2.75 years):  Primary: Composite of clinical deterioration of symptoms, fatal or non-fatal cardiovascular events, lower limb arterial surgery or angioplasty and amputation  Secondary: individual components of primary composite LIMB Presented at ACC Scientific Sessions 2005 2,078 patients, age ≥ 40 years, with objectively confirmed peripheral arterial occlusive disease (PAOD), ankle brachial index (ABI) of 0.3-0.8, and Fontaine stage II Placebo controlled. Randomized. Blinded. Mean age 61 years. 18% female. 2,078 patients, age ≥ 40 years, with objectively confirmed peripheral arterial occlusive disease (PAOD), ankle brachial index (ABI) of 0.3-0.8, and Fontaine stage II Placebo controlled. Randomized. Blinded. Mean age 61 years. 18% female. Buflomedil 300 mg BID or 140 BID if serum creatinine clearance < 40 ml/min n=1043 Buflomedil 300 mg BID or 140 BID if serum creatinine clearance < 40 ml/min n=1043 Placebo n=1035 Placebo n=1035

3. www. Clinical trial results.org Presented at ACC Scientific Sessions 2005 Primary Composite Endpoint: Clinical deterioration of symptoms, fatal or non-fatal cardiovascular events, lower limb arterial surgery or angioplasty and amputation LIMBLIMB Baseline clinical characteristics were similar between the treatment groups, with a median ABI of 0.64 and median initial claudication distance of 250 mBaseline clinical characteristics were similar between the treatment groups, with a median ABI of 0.64 and median initial claudication distance of 250 m The primary composite endpoint occurred less frequently in the buflomedil compared with the placebo (9.1% vs 12.4%)The primary composite endpoint occurred less frequently in the buflomedil compared with the placebo (9.1% vs 12.4%) Hazard Ratio [HR] 0.91 p=0.019

4. www. Clinical trial results.org Presented at ACC Scientific Sessions 2005 Secondary Endpoints: Individual components of primary composite LIMBLIMB Secondary endpoints favored buflomedil but did not reach statistical significance Symptomatic deterioration of PAOD p=0.09 Amputation of lower limb p=0.24 Cardiovascular death p=0.21

5. www. Clinical trial results.org Presented at ACC Scientific Sessions 2005 There was no difference in total death, MI, or stroke among the two treatment groupsThere was no difference in total death, MI, or stroke among the two treatment groups LIMBLIMB Fatal or Non-Fatal Cardiovascular Events p=0.40 p=0.75 p=0.44

6. www. Clinical trial results.org Presented at ACC Scientific Sessions 2005 Median initial claudication distance increased 42.9% from baseline to last visit in the buflomedil group and 0% in the placebo groupMedian initial claudication distance increased 42.9% from baseline to last visit in the buflomedil group and 0% in the placebo group Median ABI increased 9.2% from baseline in the buflomedil group and decreased 3.6% in the placebo groupMedian ABI increased 9.2% from baseline in the buflomedil group and decreased 3.6% in the placebo group LIMBLIMB Median increase in initial claudication distance, from baseline to last visit Median increase in ABI, from baseline to last visit

7. www. Clinical trial results.org Among patients with peripheral arterial occlusive disease, long-term treatment with the vasoactive drug buflomedil was associated with a reduction in the primary endpoint of fatal or non-fatal cardiovascular events, lower limb arterial surgery or angioplasty and amputation compared with placebo.Among patients with peripheral arterial occlusive disease, long-term treatment with the vasoactive drug buflomedil was associated with a reduction in the primary endpoint of fatal or non-fatal cardiovascular events, lower limb arterial surgery or angioplasty and amputation compared with placebo. Presented at ACC Scientific Sessions 2005 LIMBLIMB