February 23 rd 2009 CREATING BREAKTHROUGH DRUGS TO TREAT BRAIN DISEASES March 6, 2009Confidential ASENT Annual Meeting 2009 New Peptide Engineered Compounds able to cross the blood-brain barrier to treat brain diseases

March 6, 2009Confidential Many drug candidates (mostly biologics) have been identified BUT they do not cross the BBB Angiochem’s technology platform allows for the synthesis of novel drug candidates which are designed to cross the BBB; Using this platform AngioChem has developed a portfolio of drug candidates reaching therapeutic concentration in the brain which have been validated in animal models and in human clinical trials

March 6, 2009Confidential AngioChem’s Solution for Crossing the BBB We identified the consensus sequence of amino acid responsible for binding to the LRP receptor, which naturally transports proteins to the brain We design new chemical entities incorporating that sequence which have the ability to bind to LRP and cross the BBB physiologically

March 6, 2009Confidential LRP Receptor and Major Ligands  2- Macroglobulin ß  Thyroglobulin RAP Angiopep TPA (tissue plasminogen activator) Lactoferrin LRP transport small and large molecules LRP is highly expressed at the surface of the BBB LRP has a very fast endocytosis rate t 1/2 (~30 sec) LRP is robust and has a high capacity

March 6, 2009Confidential Development Pipeline DISCOV.PRECLIN.PHASE 2PHASE 1/2 ANG-Cytotoxic ANG 1005 : Antimicrotubule Primary (glioma) and metastatic brain tumors Undisclosed MAb Neurodegenerative diseases ANG-Peptide ANG-siRNA Undisclosed siRNA Neurodegenerative diseases DNA intercalation ANG-MAb GLP-1 receptor agonist Metabolic diseases Internal Program Joint Research Collaboration with Partner Leader in the Field Situation in 12 months from now STATUS Internal Program Joint Research Collaboration ANG Leptin Peptide Topoisomerase II inhibitor

February 23 rd 2009 CREATING BREAKTHROUGH DRUGS TO TREAT BRAIN DISEASES March 6, 2009Confidential Proof of concept Brain Uptake

March 6, 2009Confidential Brain Uptake of Engineered Peptides Compounds  ENGINEERED PEPTIDES WITH CY5.5  CAPILLARIES STAINED WITH VESSEL GREEN (FITC-LECTIN)  NUCLEI OF BRAIN CELLS STAINED WITH DAPI BLUE

March 6, 2009Confidential Homogenous Uptake of ANG1005 in the Brain 37.2 nCi/g nCi/g 20.9 nCi/g 28.6 nCi/g 22.8 nCi/g 28.6 nCi/g

March 6, 2009Confidential Angiochem products Shows Superior Brain Uptake DrugBrain K in (mL/s/g)Reference Glucose9.5 x 10-3Mandula et al.(2006) ANG ± 0.6 x 10-3Q. Smith, present work Ang-GLP-1 receptor agonist8.8±1.1 x 10-4Internal work Morphine1.6 x 10-4Seelbach et al. (2007) Ang-siRNA1.1 ± 0.1 x 10-4Internal work Insulin Rec Antibody1 ± 0.3 x 10-4Pardridge (1997) Paclitaxel and Doxorubicin ~5 x 10-5Muldoon et al. (2007) RAP1.0 ± 0.1 x 10-5Pan (2004) Etoposide~4 x 10-6Muldoon et al. (2007) TNF-α4.3 ± 0.1 x 10-6Pan (2002) Vasopressin2.5 ± 0.1 x 10-6Tanabe (1999)

March 6, 2009Confidential ANG1005 : Activity in Glioblastoma compared to Paclitaxel Day 17 Vehicle Day 24 Paclitaxel ANG1005 Day 10 Rat Brain MRI

February 23 rd 2009 CREATING BREAKTHROUGH DRUGS TO TREAT BRAIN DISEASES March 6, 2009Confidential Proof of concept Clinical

March 6, 2009Confidential ANG1005 Phase 1 Clinical Program Two Protocols Conducted in Parallel in 9 centers in the USA  ANG1005-CLN-01: A Phase I, Open-Label, dose escalation study of ANG1005 in patients with Malignant Glioma and a surgical sub-study where patients are dosed prior to surgical debulking (level of product is measured in the extracted tumor)  ANG1005-CLN-02: A Phase I, Open-Label, dose escalation study of ANG1005 in patients with Solid Tumors and Metastatic Brain Cancer

March 6, 2009Confidential Clinical Highlights Limiting toxicity Bone marrow (mostly neutropenia) No CNS Toxicity Neurocognitive results are negative to date (n=18) Immunogenicity Results are negative for antibodies to date (n=31) Validation in Humans Data collected from the clinical trial confirm preclinical data and strongly validate the platform technology. These data will be published in a peer reviewed journal.

March 6, 2009Confidential Beyond the Blood Brain Barrier BBB CROSSING AHEAD