1. The BLAST TrialBiorestLiposomal Alendronate with Stenting Study Targeted Anti-Inflammatory Systemic Therapy for Restenosis Shmuel Banai, MD Tel Aviv medical Center Tel Aviv, ISRAEL

2. Background BLAST: A Phase II dose-finding, randomized, multi-center, prospective, double blind study of the novel drug BIOrest LABR-312. N=225 Patients. PI: Prof. Shmuel Banai BIOrest LABR-312: A novel IV anti-inflammatory drug able to transiently modulate systemic monocyte function following angioplasty in a highly selective manner Hypothesis:Modulation of systemic and local inflammation will attenuate intimal hyperplasia after BMS implantation Endpoints: In-Stent Late Loss (primary) with pre-specified subgroups based on inflammatory status (Diabetes and baseline monocyte count)

3. Main Safety and Efficacy Findings Safety: No statistical difference between placebo and treatment groups in MACE, Death, MI or clinically driven TLR No specific safety concerns related to the study drug Efficacy: No statistical difference between the placebo and treatment groups in average values of Late Loss, MLD, %diameter stenosis or IVUS % volume obstruction

4. Same Average, Different Distribution Differential Patient Response : Gaussian Single peak : Non-Gaussian Left-skewed/double peak

5. Protocol mandated sub-group analysis Based on inflammatory state Diabetes: 27% Reduction in Late Loss in Diabetics. p = 0.16 Baseline monocyte count: 33% Reduction in Late Loss in patients w/ high monocytes @ baseline (50% of the entire cohort). p = 0.03

6. Conclusions There were no safety concerns associated with BIOrest LABR-312 In the total study cohort, LABR-312 had no overall effect on in-stent Late Loss, the primary endpoint In the pro-inflammatory patients (mandated subgroup analysis including >50% of the cohort), there was a statistically significant and clinically meaningful reduction in Late Loss with LABR-312 This differential response could be identified and predicted a-priori, providing the potential for personalized medicine Future clinical trials will focus on the documented clinical effect in pro-inflammatory patients